Endocrine Flashcards
Androgen insensitivity syndrome, why do females often still develop breasts? Uterus / cervix? What is recommended?
Partial or complete lack of response to androgens. Have testis which produce Mullerian inhibing substance - inhibits grown of uterus and cervix -> BLIND ENDED VAGINA.
Fetus may not develop male external genitalia or secondary sexual characteristics at puberty.
Breasts often develop due to the peripheral conversion of circulating androgens to oestrogens
Reccomended orchiectomy due to risk of testis Ca
What is ashermans syndrome ?
Intrauterine adhesions from previous infection / scarring
[Think that dam surgeon Ash who made loads of scarring -> ASH-err-man
How to differentiate between androgen insensitivity syndrome and Mullerian agenesis?
Testosterone levels - RAISED in AIS [normal male levels]
Karyotype - XY in AIS
Who commonly gets secondary amenorrhoea
Endurance athletes
Breakdown some causes of amenorrhoea in women
Physiological - Constitutional delay, exercise/stress
GU malformations - imperforate hymen, transverse septum, absent vagina/uterus
Endocrine - HYPER/HYPOthyroid, PITUITARY (Hyperprolactinaemia, cranial irradiation, Sheehans, hypopituitarism Eg after TBI), Cushing, PCOS.
Genetic - Turners
Iatrogenic - chemo/radio
What is Sheehan’s syndrome?
Pituitary infarction after major obstetric haemorrhage
Seondary Amenorrhea + evidence of androgen excess eg hirsutism/acne. Differentials
PCOS
Cushing’s
Late-onset congenital adrenal hyperplasia
androgen-secreting tumours [RARE]
What might red/thin vaginal mucosa mean
Decreased oestrogen levels
Secondary Amenorrhea with high levels of FSH/LH? What would testosterone and prolactin levels be?
Indicates ovarian failure
NORMAL prolactin / tesoterone
When to refer girls with primary Amenorrhea
No secondary sexual characteristic - Age 13
With secondary characteristics - Age 15
Worries about anything else…
MEN 1 features? Genetic? Most common presenting factor
Pancreatic neuroendocrine tumours
Primary hyperparathyroidism
Pituitary adenomas
Dominant - chromosome 11
Usually present with HyperCalcium [due to hyperparathyroidism]
Familial hypocalciuric hypercalcaemia syndrome.
Inheritance? Abnormalities in blood?
Dominant
Raised serum Ca, raised PTH
[Obvs LOW ca urine]
MEN2a gene? features? differneces to MEN
RET gene - chromosome 10
Primary hyperparathyroidism - Usually due to an adenoma [MEN1 is usually generalised hyperplasia]
Often have pheochromocytoma +/- thyroid Ca
[DO NOT get pituitary adenomas or pancreatic neuroendocrine like in MEN1]
What is pseudohypoparathyroidism
caused by resistance to PTH
->Low PO4 and Ca levels [+raised PTH]
Important management in MEN2
Prophylactic thyroidectomy
GENETIC COUNCILING
Difference between MEN2 A and B
B - gets a marfanoid appearance and mucosal neuromas
Investigations for diagnosis of phaeo? Specific scan type?
24-hr urinary catecholamines
MRI
MIGB scan (metaiodobenzylguanidine)
Investigation for medullary thyroid Ca
Elevated calcitonin
US and fine needle aspiration
Ix for likely acromegaly? Why is it good
IGF-1 (then confirmed by glucose tolerance test + pituitary MRI, visual fields, cardiac assessment…)
Has a long half-life, and can be measured at any time of day
-> Can use for assessment of recurrence
A less common cause of acromegaly (not pituitary adenoma secreting GH)?
Carcinoid tumour elsewhere
What causes pseudo acromegaly? Drug?
Insulin resistance - associated with hyperinsulinaemia / minoxidil (antihypertensive and male pattern balding)
Non surgical options for acromegaly
Radiotherapy - may end up with panhypopituitarism
Drugs
Dopamine agonists: Bromocriptine and -goline / -golides
Somatostatin analogues: ocretide
Micro vs Macro prolactinoma
Smaller or bigger than 1cm …..
Management of macroprolactinomas
Usually a dopamine agonist (most common is CARBEGOLINE or bromocriptine)
3 most common causes of raised prolactin
Prolactinomas
hypothyroid
Drug-induced - eg antipsychotics / dopamine antagonists (metoclopramide)
[Pregnancy, stress, breast stimulation, head injury, Cushings, cirrhosis]
Diabetic who is high risk CV disease and on metformin should get
A -flozin (SLG2 inhibitor)
Eg canagliflozin
What is Acanthosis nigricans? what does it indicate?
dark, thick, velvety skin in body folds and creases. It often appears in the armpits, groin and back of the neck.
Insulin resistance - DIABETES
Metformin + what if patient is OBESE and HBa1c raised on monotherapy
DPP4 inhibitor
-gliptin - eg sitagliptin
Pseudohypoaldosteronism syndrome name? What happens
Gordon syndrome
Failure of response to aldosterone -> Aldosterone levels are RAISED
-> High blood pressure, HYPERKALAEMIA, raised aldosterone, hyperchloremic metabolic acidosis
[Usually have physical abnormalities / low IQ]
What is addisons? Usual symptoms if not in crisis
Primary adrenal insufficiency
->low cortisol / aldosterone
Vauge - hypotension, GI discomfort, Weight loss, skin pigmentation
Bartter syndrome basic? Seen on bloods?
Autosomal recessive Salt wasting tubulopathy
Hypokalaemia
raised renin and aldosterone
Raised urinary cA
Conns syndrome is? - bloods?
Primary hyperaldosteronism [excess]
Hypokalaemia, low renin
HYPERTENSION
Gitelman syndrome basics?
Autosomal recessive hypokalemic salt wasting tuberopathy
Hypokalemic metabolic alkalosis
HypoCa, hypoMg
Which cells secrete renin? What stimulates this?
Juxtaglomerular cells
Reduced perfusion pressure to kidney [detected by pressure receptors in afferent arteriole]
Reduced Na in distal convoluted tuble
[Detected by macula densa cells]
Sympathetic stimulation of B1-adrenic receptors
What does renin do?
Renin converts angiotensin (produced in liver) to angiotensin I
What converts angiotensin I to II? Where is it produced
ACE
Produced in vasculature of lungs and kidney
Angiotensin II effects on organ systems
Renal?
Vasculature?
Pit?
Neuro?
Vessels: Binds to G-coupled protein receptors
-> vasoconstriction
Kidneys:
-Proximal convoluted tuble -> Increase Na reabsorption
-Adrenal cortex -> stimulates aldosterone
-Efferent arteriole -> constricts and increases pressure (increases GFR)
Pituitary
-Releases ADH
Nervous system
-Sympathetic - increases noradrenaline formation
-Hypothalamus - increases thirst -> water intake
What does aldosterone do? Where?
Acts on distal convoluted tubules
Na reabsorption, K+ excretion
[Increases osmolarity in blood -> increased volume from extracellular]
Uptake on 99Tc Thyroid scintigraphy in Graves? adenoma? throiditis?
Increased GLOBALLY in graves
Increased FOCALLY in adeoma / toxic multinodular
DECREASED in thyroiditis
[stored thyroid hormone (t3/4) gets released which causes a decrease in TSH -> reduced uptake as TSH synthesis is decreased]
When are TPO thyroid antibodies positive
95% in Hashimotos
70% in graves
20% in normal population
The most common cause of secondary hypothyroidism
Tumour secreting TSH
What antibodies are found in graves
IgG autoantibodies - eg TSH-receptor antibody
[Anti thyroglobulin, anti microsomal]
Causes of normal t3/4 with low TSH
Thyroxine excess
Steroid therapy
Dopamine infusion
non-thyroidal illness
Drugs used in hyperthyroid? Side effects
Carbimazole, propylthiouracil
Common - rash, leukopenia
Rare - agranulocytosis, aplastic anaemia, hepatitis, vasculitis (propylthiouracil)
Rapid control of symptoms in hyperthyroid
B blockers / CCBs
What are the 2 types of DI and what happens?
Cranial - failure to secrete vasopressin from posterior pituitary or; Nephrogenic resistance to vasopressin within the kidney
Common electrolye causes of nephrogenic DI ? Drug? Management?
Electrolyte - HyperCa, HypoK
Lithium
Treat cause. Or try Bendroflumethazide
Where does ADH (vasopressin) work
Collecting ducts - increases water resorbsion
Pathogenesis of cranial DI
Need to damage hypothalamic nuclei (supraoptic and paraventricular).
Damage to the posterior pituitary doesn’t cause it as it can be secreted directly from the hypothalamus
Plasma / urine osmolalities in DI vs psychogenic polydipsia?
Differentiate cranial / nephrogenic DI?
DI - HIGH plasma, Low urine
PsychoP- Low plasma, low/normal urine
Cranial - low plasma levels of ADH
Nephrogenic - high plasma levels of ADH
Check osmolalities post DDAVP (Desmopressin)
Cranial DI -> High/normal urine osmolality
Nephrogenic DI - Stays the same
Management of nephrogenic vs cranial DI
Nephrogenic - treat cause. Then Bendroflumethazide
Cranial - desmopressin
Women with diabetes who become pregnant advised to take what?
5mg folic acid daily
Diagnosis of gestational diabetes?
Fasting glucose >5.6
two hour glucose of >7.8
Then confirmed with oral glucose tolerance test
Who would you test for gestational diabetes
Previous GDM
2+ glycosuria on 1 occasion, 1+ on 2 occasions
Any risk factor:
-BMI >30
-Previous macrosomic baby >4.5kg
-First degree relative with DM
-South asian / middle eastern / afrocaribean
Antihyperglycaemics for GDM
Diet and lifestyle first -OBVIOUSLY
1st line - Metformin
2nd - Glibenclamide - (sulfonylureas)
3rd - insulin
Why do babies with diabetec mums get macrosomic ?
hyperglycaemia -> B-cell hyperplasia in islets of langerhan pancreatic cells -> increased insulin
Insulin is a growth promoter
Why do babies of diabetic mothers get more respiratory distress syndrome?
Surfactant deficiency
Metformin (and Glibenclamide) are the only oral antihyperglycaemic medication that is safe in pregnancy. Which common meds need to be stopped?
ACEi
A2A inhibitors
statins
Delivery of baby with GDM should be planned for when?
37-38 weeks IF ON Treatment
otherwise 40+6 if diet controlled
When cord is cut in baby with GDM what do you need to ensure?
What extra risks are in babies who are small for gestational age?
Constant glucose infusion which can be weaned down
Low fat/gyclogen stores -> risk of hypothermia and high insulin levels as they are used up.
When is insulin used first line in GDM
Fasting glucose >7
Fasting glucose >6 with complications such as macrosomia / hydraminos
Or later in preganacy:
fetal abdo circumfrence >95th percentile
Pre prandial >6.5, post prandial >7.5
When to start a sliding scale in labour
if Glucose >6
Hypoglycaemia in neonate Rx?
Feeding bottle / tube
if innefective add buccal dextrose
If ineffective -> IV dextrose
Fasting glucose <7 with no fetal complications? 1st line Rx
diet and exercise
(review in 1-2 weeks)
Who gets aspirin in pregnancy
Those at risk of pre-eclampsia
Either 1 high risk, or 2 moderate risk factors
High:
CKD, Autoimmune diseases eg SLE/APS, Diabetes, Hypertension or previous gestational hypertension
Moderate :
First preganacy, preganacy interval >10years, >40 years old, BMI >35, Twin/multiple, FHx of pre-eclampsia
Raised urinary Ca
hypokalaemia
Metabolic alkalosis
raised renin / aldosterone
Normotensive/Low
Barttler syndome
Hypokalemic metabolic alkalosis
HypoCa, hypoMg
Hypocalsuria
Gitelman syndrome
Hypertension
Hypokalaemic metabolic acidosisĺ
Liddle syndrome
Hyperk ECG
Tall t waves
flattened / absent P waves
Prolonged QR
HypoK ecg
Flat / inverted T waves
Prolonged PR
ST depression
Tall U waves
Triad of phaeochromocytoma
Hedaches, palpitations, sweating
Who gets bilateral familal phaeochromocytomas
MEN syndrome (bilat phaeos in 70%)
Cafe-au-lait patches and phaeo
Neurofibromatosis
Definitive management of phaeochromocytoma is surgery. What do you use pre op? What do you need to be careful with?
A blocker Eg Phenoxybenzamine - gives blood volume explansion
Then can add in a B blocker - DONT give before a-blocker as risk of hypertensive crisis due to unrestricted alfa stimulation
Urine test to differentiate T1/T2 DM
Ketonsuria - indictive of insulinaemia
Hashimotos thyroiditis test
Anti TPO
Also raised in Graves
Hypokalaemia
Metabolic alkalosis
Resistant hypertension
Primary hyperaldosteronism (Conns)
Will have a raised aldosterone:renin level
Why does low body weight lead to ammenorrhoea
-> Reduced FSH/LH and sedondary ovarian failure
Management of sheehan syndrome
Steroids immediately
Then full endocrine assement and replacement of other pit dependent hormones Eg thyroxine….
Sheehan syndrome… Features of hormone deficiencies
Fatigue and low muscle mass - GH
Low BP, cold intollerance and weight gain - TSH
Hypotension, hypoglycaemia - ACTH
Galactorrhoea - Prolactin
Ammenohhroea - FSH / LH
How to seperate pituitary and adrenal cushings syndrome? NOT using an MRI ya cheeky bastah.
BOTH will have lowered cortisol levels if given dexamethasone
Only pituitary (cushings disease) will be affected by corticotropin releasing hormone (cortisol increases)
What is cushings disease
Bilat adrenal hyperplasia secondary to ACTH secreting pituitary adenoma
2 tumours which often cause ectopic cushings syndrome
Small cell lung
Carcinoid
ACTH levels in adrenal adenoma ?
In pituitary adenoma?
LOW due to negative feedback
High in pit - that’s the tumour dipshit
Steps for diagnosis / working out where cushings is from..
Step 1 - Dexamethasone supression test OR 24hr urinary cortisol test
Step 2 - High dose dex supression test [0.5mg QDS for 2 days] then measure cortisol
-In normal people this will suppress to <50nmol/L
-ACTH will be -Normal/raised in pituitary or ectopic ‘ACTH dependent’
-ACTH will be low or non detectable in Adrenal
Step 3 - Localisation
Low/no ACTH - CT/MRI adrenals
Has ACTH - to differentiate between pit and ectopic -> High dose dexamethasone test.
-Cortisol will be raised if pituitary -> MRI
-Cortisol unaffected -> CT TAP with contrast
Who might get a positive dex supression test (PSEUDO-cushings) - therefor you need the high dose one to confirm diagnosis?
Obese, depression, alcoholic, liver enzyme inducers
Drug to normalise cortisol levels if surgery for cusings not possible
Metyrapone
Bilat adrenalectomy has what risk? Presentation
Nelson syndrome
Bilat adrenalectomy -> pit enlarges as loss of legative feedback on ACTH
-> Skin pigmentation common
-> Supression of other pit hormones / features of mass effect
Weight loss, nausea, lethargy, hypoNa, HyperK, hyperCa, Raised TSH, Postural hypotension, skin pigmentation / vitiligo,
Addisions
Most common cause of hypoadrenalism
Long term steroid use
[Then addisions]
Addisons is? Antibodies? Associated with? Other diseases which cause primary hypoadrenalism?
Autoimmune destruction of adrenal glands
Adrenal autoantibodies
Vitiligo - commmon [Also in other automimmune tho]
TB/HIV/adrenal haemorrhage / Congenital hypoadrenalism (21 hydroxylase deficiency)
21-hydroxylase deficiency is often misdiagnosed as?
Primary hypoadrenalism
[Same same but different cause to addisons]
What does aldosterone do in the kidney? [Pathophysiology of addisons]
Sodium retention and excretion of potassium
Addisons bloods
hypoNa, HyperK, hyperCa, Raised TSH, hypoglycaemia, raised urea,
Gold standard test for addisons? Briefly explain it and what values you arelooking for
Short synacthen
Inject 250mcg ACTH -> Plasma cortisol >550 after 30-60mins
Or rise of >200
Is normal
In Addisons they unable to make it
What needs replaced in addisons Rx
Steroids
Both glucocorticoids and mineralcorticoids
Eg hydrocortisone + fludrocortisone
Who gets thyroid eye disease? Key risk factor? Can you have normal TFTs
Graves usually
SMOKERS
yes 10% euthyroid
Thyroid eye disease brief pathophysiology?
Ix?
Throid stimulating hormone receptor (TSHR) + IGF-IR are expressed in thyroid/adipocytes/fibroblasts
-> Get simulated by TSHR autoantibodies / activated lymphocytes
->Fibroblast proliferation + water retention + increased orbital muscles -> Thyroid eye disease
CT/MRI
TSHR antibodies
Treatment for thyroid eye disease? Which thyroid treatement to avoid?
Smoking cessation
High dose steroids
IF reduced vision / colour differentiation (optic nerve dysfunction) -> urgent decompression surgery
AVOID radioiodine treatment - can make worse
What Ca often leads to SIADH? Biochem + urine findings?
What else do these tumours often secrete?
Small cell
SIADH -> HypoNa
LOW plasma osmolarlity
HIGH urine osmolarity with HIGH urine Na
ACTH
Common tumour secreting what leads to Hyper Ca
Squamous cell secreting parathyroid hormone related protein
Prolactinoma -> Ammenorrheoa. WHY?
Prolactin inhibits GnRH though negative feedback.
-> Reduced secretion of FSH/LH from anterior pituitary
-> Hypothalamic hypogonadism + secondary ammenorrhoea
Dyslipidaemia
Hairloss , fat, dryskin
Need to check?
THYROID function.
90% of hypothyroid have dyslipidaemia - usually HIGH LDH + total cholesterol
2 key Drugs that cause hypothyroid
Amoiodarone
Lithium
Demeclocycline use?
Drive free water excretion in patients with SIADH
Wilson disease is serum caeruloplasmin low or high? Inheritance?
Drug for Rx
Low
Recessive [ATP7B gene]
Penicilliamine [BUT mostly jsut avoidance of copper containing foods]
When might you think a diabetes presentation is MODY
Strong family history
MODY - 2 most common types and gene
MODY 2 - Glucokinase gene
20% - Mild form with minimal complications
MODY 3 - HNF-1a
60% - Progressive beta cell failure. Very Sensitive to sulfonyureas Eg Gliclazide
What is De Quervain’s
subacute) thyroiditis usually triggered by a viral infection Eg mumps / flu
Usually PAINFUL and rapid swelling unlike autoimmune causes
Breifly on primary secondary and tertiary hyperparathyroidism? Levels of Ca? PTH? PO4?
1 - Adenoma, usually present with symptoms of HyperCa. [BONES STONES MOANS GROANS]
[seen in POST MENOPAUSAL WOMEN]
Ca - RAISED, PTH - High or inappropriately normal, PO4 LOW
2 - Parathy glands undergo hyperplasia due to longstanding HypoCa [Usually Caused by longstanding CKD. Or sometimes malabsorbtion / vit D deficiency]
Presents with CKD
Ca - LOW, PTH- Raised, PO4 High in renal disease, PO4 low in Vit D deficiency
3- After prolonged longstanding secondary HyperPTHism [CKD]. Glands lose negative feedback loop and keep secreting PTH despite Ca being normal / high
Ca - Raised, PTH - raised, PO4 usually raised
Presents with symptoms of hyperCa
Trigger for PTH secretion? What does it do?
Secreted in response to low Ca levels
a) Increases osteoclast activity -> Release Ca + PO4 from bones
b) Increases absobtion of Ca and REDUCED PO4 from kidney
c) Increases Vit D3 production
Bar hyperPTH, some other causes of HyperCa
1 - familial benign hypocalciuric hypercalcemia
Dominant inheritance. HyperCa and normal / mildly raised PTH
[Due to loss of gene which senses Ca levels in PTH -> more PTH and less urinary excretion]
2 - Drug induced. Lithium, thiazide
3 - Sarcoidois
Drugs causing hyperCa
Lithium
Thiazide
Osteolysis, bone tumours, pepper pot skull
Some parathyroid ca xray buzz words
Management of mild primary HyperPTH
Hydration
Avoid Thiazides / lithium / high VitD/Ca intake
When would you surg mananage primary-HyperPTH?
2 - KEY complications
ANYONE with complications or <50
[Raised Ca
Bone disease
Renal calculi
Imapaired renal function
<50 ]
Hypoparathyroidism
Recurrent laryngeal nerve damage
Rx of secondary hyperPTH
Correct VitD if low
CKD Rx
-PO4 restriction/binders
-Ca supplement
Tertiary HyperPTH Rx
Cinacalcet if crumbly
Subtotal/total parathyroidectomy is recommended
Indications for surgery for toxic multimodular goitre
> 80g
Symotoms of neck compression
Co-existing HyperPTH needing surgery
Need for rapid correction of hyperthyroid state
Antihypertensive classes which impair glucose tollerance?
Thiazides
Non cardioselective B blockers. [Bisoprolol/Carvedilol are fine. Propranolol less so]
Medication class to reduce progression of diabetic peripheral neuropathy?
ACEi - even if normotensive
What are thionamides?
Antithyroid drugs
Carbimazole, Propylthiouracil
What is more protective of osteoporosis? Being fat or being active?
Being FAT bmi 25-30 - [Without having diabetes]
Is having a baby beneficial or bad for osteoporosis in later life
BABY = good - 4x less osteoporosis in later life
Oral contraceptives - which protect against osteoporosis?
COCP
[POP - does not]
Medullary thyroid Ca is in which syndrome?
Other bits
MEN 2a
1-Medullary thyroid Ca
2- Phaeochromocytoma
3- HyperPTH
First step in DKA
Fluid and electrolytes - people die of hypovolemia + electrolyte derangements
[IV insulin can wait a moment]
What causes congential adrenal hyperplasia? Inheritance?
Recessive - Hydroxylase defiency [90% are 21-hydroxylase]
What is 21-hydroxylase for? When you lack it? Common Biochem / examination
Synthesis of steroid hormones - eg cortisol / aldosterone
End up with CAH
[High amounts of intermediates in steroid formation Eg Androgenic hormones - testosterone / 17-hydroxyprogesterone -> virilisation / ambiguous genetalia
-> Risk of Addisonian crisis due to low aldosterone shortly after birth
The gold standard test for diagnosing CAH [21-hydroxylase deficiency]?
Corticotropin stimulation test
Pharmacological Rx of CAH? In utero?
Gluco/mineral corticoids
If salt losing -> NaCl therapy in infants
Preg - IV steroids can help with genital ambiguity
[BILAT adrenalectomy is sometimes required]
When would you use GLP-1 analouges? Contr-indications? Eg?
FAT people with diabetes BMI >35 as good for weight loss
Can’t use in gastroparesis as delay gastric emptying
-glutides Eg Semaglutide, luraglutide, dulaglutide
Uusally once daily or even once weekly
What does glucagonoma do
Cancer of pancreas -> secretes glucagon
-> Increases glucose levels by activating anabolic and catabolic processes such as gluconeogenesis and lipolysis
How does metformin work
inhibits gluconeogenesis by liver
[biguanide]
C peptide in an isulinoma
C peptide raised
(As is insulin)
Euvolaemia, hyponatraemia, low serum osmolality
Normal K, normal renal function, raised urine Na
SIADH
hyponatraemia caused by hyper or hypo thyroid
Hypothyroid [think low and slow]
Management of SIADH with minimal symptoms
Fluid restict
Management of severe hyponatraemia? Key risk of correction fast?
Drug to cause (partial) nephrogenic DI?
Hypertonic saline [or loop diuretics+ saline]
Central pontine myelinolysis
Demeclocycline - blocks ADH [induces partial nephrogenic DI]
Vasorpressin receptor antagonist - eg tolvaptin
Diabetic complication is gastroperisis. What is drug therapy of choice?
Domperidone
[second line erythromycin]
METOCLOPRAMIDE IS NO LONGER RECOMMENDED
Non-classical CAH. Drug Rx in adults with mild symptoms
Flutamide [antiandrogen]
DONT WORRY IF YOU CANT REMEBER THIS
Lithium impact on thyroid + prolactin?
Alternative drug if patient wants to get pregnant
Hypothyroid [will have raised TSH]
Raised prolactin
Lamotragine
Recurrent painful orogenital ulceration
Uveitis
Polyarthritis
What syndrome?
Rx?
Bechet
[Autoimmune disease (HLA- b12/51/52) No specific test - but can exclude other causes Eg SLE]
Topical steroids for mucocutaneous
Oral pred / azithromycin
[TNFa inhibitors in combination with pred are 3rd line or if there is GI/CNS/Vascular involvement Eg. Infliximab
Rest card
High 5 to you
Hypos with high insulin and low c peptide = ?
high c peptide?
insulin abuse
Insulinoma or sulphonylurea (gliclazide) abuse
Adrenal mass with normal urinary catecholamines and HTN.
What is the best drug for HTN? What if it is a phaeo
Spironolactone - block aldosterone
(Conns)
Phaeo - Phenoxybenzamine [doxazosin second line]
Angiotensin II and aldosterone work where
Angiotensin II - proximal convoluted tubule
Aldosterone - distal convoluted tubule
[Angiotensin comes first]
Liddle vs cons on bloods
Liddle- acidosis
Cons - alkalosis
Both HTN, hypoK
Thyroid antibodies while pregnant increase risk of
Premature and spontaneous miscarriage
Rx of severe graves with relapses and eye disease
Total (not subtotal) thyroidectomy
First line Ix in Conns
Aldosterone:renin ratio
How do the -flozins work?
SLG2 inhibitors
[SLG2 is a transporter which is responsible for 90% glucose reabsorption]
-> increased renal excretion of glucose
how do the -glutides work?
GLP-1 monoagonists (incretin mimetics)
Stimulate glucose-sensitive insulin release
Also, delay gastric emptying
How do the -gliptins work
DPP4 inhibitors
Prevent breakdown of incretin
-> Stimulates insulin release
Strong family Hx of diabtes - eg mum type 2 and brother type 1.
Otherwise normal shape no risk factors. What type of Diabetes? 1st line rx?
MODY
Gliclazide
How does metformin work?class?
Reduces hepatic glucose output
biguanides
Most common cause of secondary hypertension?
Conns
IGF-1 raised - how to confirm Acromegaly
Oral GTT and GH measurement
Blood gas of cushings
Excess glucocorticoids ->
-Potassium depletion
-Na and water retention
->Cl excretion
HypoCloraemic metabolic alkalosis
Blood gas of cushings
Excess glucocorticoids ->
-Potassium depletion
-Na and water retention
->Cl excretion
What is the short synacthen test for
Cortisol deficiency / adrenal failure
No option for overnight dex supression test. Ie want to investigate as OP what test for cushings
2x 24hr urinary cortisol
Incidental pit adenoma on CT. What is likely by 12 months
No change / Sx - 75% of incidental remain unchanged
New diagnosis of hypothyroid. How long after starting thyroxine do you need to wait to check levels?
1 month
Most common cause of Hypothyroid worldwide
iodine defiinecy
Poor controlled diabetes -> burning / aching / proximal weakness = ? Rx?
Diabetic amyotrophy
(Proximal neuropathy, lumbosacral plexopathy)
Improve glycaemic control Eg insulin
Diabetes, then develops yellow lesion (usual shin) that grow slowly over years -> may ulcerate =?
Necrobiosis lipoidica
Breasts and no pubes
Androgen insensitivity syndrome
Best drug class to protect kidneys with diabetes
ACEi
Which diabetic drugs promote weight loss? If IBD which needs to be avoided
GLP-1 (Glutides)
Liraglutide contra indicated in IBD
Gitelman blood gas? Differentiate from barter?
Hypokalaemic metabolic alkalosis
Gitelman has low urinary Ca
Differentiate MEN and MEN 2 and MEN 2b
MEN - Pit
2a - phaeos
2b - marfan
Diabetic on metformin
FAT, hypertensive, Prev MI. Which additional agent?
SLG-2 inhibitor
-gliflozins
(Good For heart)
then could add a GLP-1 (eg glutide) for weight loss after
GLUTide (glutinous)
Obese on gliclazide with shite kidneys. hba1c still high
GLP-1
-Eg dulaglutide
What is seen in 95% of MEN1 sufferers
HyperParathyroidism
When to use Throid isotope uptake scanning?
Differentiate causes of hyperthyroidism
What test to initially assess size of thyroid gland
US
CT is used to asses tracheal compression if required
HHS what would you expect BM / Bicarb / ketones / pH / serum osmolality to be
BM high >30 but likely at least 50
Bicarb <15
Ketones - none / 1+
pH - >7.3
Osmolality high >320
What causes thyroid eye disease
Glycosaminoglycan (GAG) deposition
[fibroblasts stimulated by anti-TSH antibodies and activated T cells.
->GAG deposits which are hydrophilic and therefore draw in oedema]
Dyslipidaemia - what do you always need to exclude
Hypothyroidism
Sarcoid on steroids. Presents with polyuria/dipsia =
Cranial DI
Sarcoid well known cause of cranial DI
Why does weight loss cause amenorrhoea? What about low body weight?
Weight loss -> increased ghrelin
->Inhibits hypothalamic-pituitary-ovarian axis
Low body weight -> low levels of leptin (stored in fat cells)
Which then also inhibits the axis
Skin finding specific to graves ? Pathophysiology?
Pre-tibial myxoedema
(due to accumulation of glycosaminoglycans (GAGs)
Long term use of what drug may cause PCOS
Sodium valproate
Diagnosis of PCOS
2 out of 3 of:
-US (Ideally transvaginal)
-Clinical/biochem features
-Oligo/ammenorrhea
LH/FSH in PCOS
LH:FSH ratio is high
Best drug for androgenic acne in PCOS
Co-cyprindiol
(cyproterone acetate and ethinylestradiol)
Stimulate ovulation in PCOS
Clomifine
Which drug causes euDKA
SGLT2 inhibitors
-gliflozins
Chemical for pear drop smell in DKA?
Cause of lingering acidosis after 36hrs
Acetone
Lingering acidosis: beta-hydroxybutyrate
The most important thing for fetal protection and mum with diabetes
Tight glucose control
amiodarone induced thyrotoxicosis Rx
steroids and antithyroid drugs
antithyroid drugs in preg
propylthiouracil for most
Then switch to carbimazole in late pregnancy to prevent material liver toxicity
[Often can just observe if only minor increase in t4]
Squamous cell Ca, narrowed QT on ECG and drowsy
Hypercalcaemia (from PTH related peptide)
PCOS Levels of:
LH
FSH
Testosterone
Oestradiol
LH - high
FSH - normal
Testosterone - high
Oestradiol - normal
Normal/Raised TSH with raised t4/t3. Ix needed?
MRI pituitary
What do you need to replace in turners syndrome
Oestrogen
Weirdly what can worsen diabetic retinopathy?
Rapid improvement in BM control
Postpartum thyroiditis antibodies
Anti-TPO (same as hashimotos)
3 Main enzyme deficiencies in CAH? Which have high androgens? Which causes HTN? Low cortisol?
21-hydroxylase
-Raised androgens -> masculinisation and early pubity
-Salt wasting (similar to addisons)
11b-hydroxylase
-Raised androgens
-HTN
17a-hydroxylase
-Low androgens -> ambiguous genitalia / undescended testis
-HTN
ALL 3 get low cortisol
When would you be concerned about normal PTH
Raised CA - may indicate PT cancer
Or tertiary hyper PTH
How does tamoxifen work on oestrogen receptors ?
Mixed agonist and antagonist (depending where the receptor is)
it is a selective oestrogen receptor modulator (SERM)
When can a diabetic on insulin drive HGV?
NO Hypos for 12 months
Or if just started need 3 months of regular BM monitoring
What type of renal tubular acidosis do people with autoimmune conditions get?
Type 1
(hypokalaemic)
Fat and poor controlled diabetes - when can they not get a glp-1 analogue?
EGFR <30
(Same for metformin and DPP4 inhibitors)
Which is the only DPP4 inhibitor licensed for eGFR <30? [Remeber none of the GLP-1 are allowed either]
Linagliptin
Fall in whcih hormone leads to endometrial shedding?
Progesterone
Primary hypertriglyceridaemia has which raised which lipids? Key risk?
VDL -> CV risk
If not treated alos high risk of pancreatitis
Shortening of 4th/5th metacarpals, short stature. Why seizures? Seen on CT head?
Pseudohypoparathyroidism
Low Ca -> seizures
Calcification of basal ganglia
[Will have raised PTH as defect in PTH receptor in bones rather than PTH production
Menorrhagia, fat and mildly increased prolactin
Hypothyroid
Differentiate PCOS and Non-/classical CAH?
Both have irregular mentrual cycles, and signs of androgenism with raised testosterone
nc-CAH - raised 17-OH Progesterone
Normal weight
PCOS - usually fat.
Classical CAH presents as salt wasting as a child
Gold standard test (not MRI) for panhypopituitarism
Insulin stress test
(checks GH and ACTH)
Hypokalaemic periodic paralysis defect in wha1?
voltage-gated calcium channel
(CACLN1A3)
Where secretes melatonin
Pineal gland (converts it from serotonin)
Sometimes adrenal adenoma can be too small to see on CT? What test can you do to localise it?
Bilat adrenal vein blood sampling [for 18-hydroxycoroticosterone]
Can see if levels are 10:1 on one side ->localises tumour
Post partum thyroiditis Rx if symptomatic
Propranolol and wait it out
Hard fibrous thyroid mass causing hypothyroidism
Reidels thyroiditis
DeQuevirans thyroiditis Rx
Propranolol and NSAID
[steroids if above fails]
Differentiate first presentation of DKA vs Adisons based on anion gap only
Addison has a normal anion gap
DKA has raised (ketones )
Features of prolactinoma and acromegaly is what?
Acromegaly (30% have raised prolactin as it is a mixed tumour)
hypothyroid and cardiac issues
Risk of cardiomegaly and effusions / Heart failure
Hard rapidly enlarging thyroid mass with lymphadenopathy is likely?
Anaplastic thyroid carcinoma
Female external genitalia, breasts but no pubs and hernia operation as an infant
AIS
Most common thyroid Ca ? If the question mentions familial?
Papillary
Medullary if familial (MEN2a)
Port-wine naevus on face with phaeo?
Sturge-weber syndrome
Known MEN1 - now new diabetes.
What rash? Why?
Necrolytic migratory erythema
Due to glucagonoma
How does metformin help in PCOS
Increases insulin sensitivity
Including to ovary -> increased chance of ovulation
PCOS LH/FSH/prolactin
Raised LH:FSH Ratio
Prolactin often mildly raised
Hypo with no IV access and reduced GCS? Mechanism and key enzyme?
IM Glucagon 1mg
Glycogenolysis in the liver by activating adenylate cyclase
Convert 5mg pred to hydrocortisone
20mg
Multiple by 4
Weight gain, poorly controlled hypertension., HypoK, impaired glucose tolerance 1st line Ix?
24hr urinary cortisol
[cushingoid features more prominent than simply conns]
Secondary HyperPTH frist line Rx
Calcium and vit D
low PO4 diet
Hereditary haemochromatosis. When would you use iron chelation?
Rx of erectile dysfunction?
Iron chelation if cant tollerate venesection (eg anaemia / cardiac disease)
Erectile dysfunction is due to endocrine dysfunction -> hypogonadotropic gonadism
-> Give testosterone
thyrotoxicosis but not graves. What might you find on exam of the eyes
Lid retraction
[due to sympathetic hyperactivity]
Headaches, collapse, hypotension, partial CNIII palsy
Pit apoplexy
[PICA aneurysm usually more unilateral CN III]
When is impaired fasting glucose?
6-6.9mmol/l
Black urine, discolour sclera and cartillage = ? Due to?
alkaptonuria
Homogentisic acid oxase deficiency
Homocystinuria due to defect in
Cistathionine beta synthase
BP target post MI? What if diabetes?
<140/90
<130/80 if diabetic / albuminuria
Sex hormone binding globulin in PCOS?
Low due to insulin resistance
Hypothyroid on thyroxine. Normal TSH, Low t4 and normal T3. what next
Nothing - adequate replacement given normal t3 NA Dtsh
What would tertiary hypothyroid look like
Low TSH and low T3/4
Started oral contraceptive -> rash on the body and some blistering. ANA positive dx?
Porphyria cutanea tarda
TSH targets following thyroidectomy
Supress TSH <0.1 for 12 months
Post radioactive iodine Rx women shouldnt get pregant for 6 months - but what else should they avoid
Avoid close contact with children or other pregnant women for 10 days
MEN 1 parathyroid issue
Hyperplasia, not malignancy
Hypertension with HypoK and supressed renin and aldosterone =
Liddle
Which Hyper/hypothyroid for increased prolactin? Decreased Oestrogenisation?
Hypothyroid
Hyper
Spotty skin pigmentation, Atrial Myexoma and endocrine tumours in?Genetic?
Carney complex
[AD chromosome 17]
How does levonorgestrel work as morning after pill ?
Delays ovulation
What is the best dopamine agonist for prolactinomas? What do you do if they become pregnant
Carbegoline
Stop it
Renal stone, episodes of sweating and palpitations, thyroid nodule. What is next Ix?
24hr urinary metanephrines
Conns renin aldosterone ratio?
Reduced renin. Riased aldosterone [Producing aldoserone
Cause of hyperCa in sarcoid?
Increased hydroxylation of vit D
Most common side effect of HRT
Breast tenderness
Glucose tolerance test in acromegaly actually measures?
75g of glucose - then measure GH level (will remain >1ng/ml)
Disseminated TB key endocrine issue
Adrenal insufficiency Eg HyperK, weaness, lethargy increased pigmentation…..
penumococcal / pseudomonal Sepsis -> HyperK, hypoNa, Hypotension and acidosis?
Adrenal insufficiency
Probably due to DIC -> adrenal haemorrhage
What haooens to 97% of insulin dependent diabtetsa after 15 years even if thier controll is excellent?
Retinopathy
Lanreotide does what
Stimulates somatostatin receptor
Raised TSH with Low end of normal t3/t4 =
Su clicnical hypothyroidsim
Diabetes + HTN. Acute visual loss in right eye. Fundoscopy shows segmenetal flame haemorrhages in lower quadrant of eye = ?
Branch rentinal vein occlusion
-Segmental haemorrhages
Rx of solitary papilliary thyroid Ca
Near toltal thyroidectomy + radioactive iodine
[then thyroid hormone replacement]
Amiodarone induced thyroxicosis Initial Rx if increased uptake and positive antibodies?
What if absent uptake and negative antibodies with destructive thyroiditis?
Propylthiouracil
[then add steroids if needed]
Steroids
Polyglandular syndrome type 1 what is the most common issue? What is difference with type 2?
HypoPTH -> HypoCa
[Adrenal insufficiency, Gonadal failure, Hypothyroid]
Type 2 - dont have HypoPTH
[Do get others above AND T1DM]
Charcots foot key Rx
Immobilisation of foot
Long-standing watery diarrhoea and acidosis. which endocrine issue could cause
VIPoma
Low Ca, Low Po4, raised ALP =
Vit D deficiency
Pharmacist with raised T4 and <0.01 TSH with low uptake on thyroid scanning =
Thyrotoxicosis fasciata
[She been scranning thyroxine]
How long before check HBA1C after 5units blood
3 months
Stange thing on blood gas of hyperthyroidism
Low PCO2
Kallman first line Rx ? If wants to have kids?
Testosterone patches
Pulsed therapy wihth GnRH analouges
1st line Rx of hyperthyroid with solitary nodule (not Ca)
Radioiodine if no contraindications
[Surg second line]
Known hashimotos, slow incresing size of goitre - which Ca?
Lymphoma
Thyroid lymphoma Rx
Cehmo radio
New diabetes, iron deficiency anaemia, weird rash
Glucagonoma
[Rash is necrolytic migratory erythema]
Bar being marfanoid what is other difference between MEN2a and 2B
2a Hyper PTH more likely
2b Phaeos even more common
What do bisphosphonates do
inhibit osteoclasts
Previous cerebellar haemorrhage, bilat renial angiomas
VHL
cerebral / retinal issues are presenting feature 40% of time
Asthma with exacerbations. Orthostatic hypotension, HypoNa, HyperK, Low 0900 cortisol which rises following synACTH =?
Steroid-induced hypoadrenalism
Why ammenorhheoa in addisons
Get hyperprolactin
Surgical cure rate in acromegally if microadeoma / macroadenoma
80% micro
40% macro
Why hyperprolactin in metoclopramide therapy
Binds to D2 receptors in pituitary lactotropes
Bopsy of pagets is only way to 100% differentiates from other mixed lytic/slcerotic malignancy - what does it show?
Multinucleated osetoclasts
HLA DR7
minimal change
HLA B47
CAH
HLA A28
Schitz
What do most autoimmune HLAs start with
HLA DR or HLA DQ
Turner genetics
45X
Superior bitemporal quadrantanopia caused by
Pit tumour
Which of the pyruvate enzymes is inhibited and which is stimulated by insulin?
Pyruvate carboxylase - inhibited
Pyruvate dehydrogenase-stimulated
[thing the other dehydrogenase enzymes tend to be stimulated by things being added Eg Adehyde / alcohol dehydrogenase]
Which hormone signals epiphyseal fusion and cessation of growth
Oestrogen
Why glucagon in BB overdose
Bypass B receptor and stimulates cAMP -> B stimulation on heart
Lasy with reflux oesophagitis who doesn’t want regular injections for osteoporosis can get
Denosumab
[IV but only once every 6 months]
Testicular feminisation is also called? Chromosomes?
When do they usually present?
What is it biochemically due to?
Androgen insensitivity syndrome
46XY but looks female
Usually present with primary ammenhorea in late teens
Due to lack of dihydrotestosterone receptors
Addison’s - anti-adrenal antibodies are also called
21-hydroxylase antibodies
Acromegaly get which Ca
Colon
Which hormone drives male secondary characteristics
Dihydrotestosterone
[testosterone for development of genitalia and spermatogenesis]
Test to confirm conns other than hypoK, raised aldosterone and low renin?
Saline suppression test
Acromegaly first line Rx
Transsphenoidal surgery
What is testosterone formed from? Oestrogen? Why feminisation in alcoholics and obese?
Testosterone formed from cholesterol
Testosterone is converted by aromatase to form oestrogen
Alcohol / obese -> increased aromatase activity = increased oestrogen
Glucokinase mutation = MODY?
HNFa
HNFb
MODY 2
HNFa - MODY 3
HNFb - MODY 5
Gets worse as prime number increases
Minimal -> symptomatic -> bilat cysts
Weight loss, worsening of T2DM control anaemia and rash over groin and lower legs
Glucagonoma
Antidiabetic which increases risk of foot fractures
Canagliflozin
[Calcanius]
Male with FSH deficiency and rasied testosterone but reduced sperm count has?
Deficiency of androgen binding proteins
What type of bone loss in osteoperosis
Trabecular
Low TSH and T4 key Ix?
Pit MRI
Significant weight gain, HTN, Hirtuism, abdominal striae… What is most likely
Cushings
Which drug abuse would mimic barter’s syndrome?
When would this be the answer rather than barter ?
Furosemide
if questions mention someone who is not presenting young Ie >25 and may be a pharmacist
Which of the GLUT transporter for:
Glucose is taken up into muscle and adipose tissue following insulin stimulation
GLUT 4
Which of the GLUT transporter for:
non-insulin stimulated uptake of glucose into adipose and muscle
GLUT -1
Which of the GLUT transporter for:
Glucose uptake into beta-cells (glucose sensing)
GLUT - 2
Which of the GLUT transporter for:
Non-insulin glucose uptake into neruones
Glut -3
Exogenous GH does what to GH-deficient. Fat/lean mass? Lipids?
Increases lean mass decreases fat mass
No impact on cholesterol / triglycerides
Post sub total thyroidectomy - how long is the HypoCa from HypoPTH expected
Transient - usually due to devascularisation of one/more of the PTH glands at the time of surgery and will recover
[Though still needs treated in the acute setting]
Identical twins - one hasT1M - risk of the other?
50%
What is the cut-off for urine osmolality for primary polydipsia following the deprivation test
> 300 mOsmol/Kg = Psychogenic polydipsia
Why sweating in acromegally
Sweat gland hyperplasia
