Acromegaly
Features (7)
- Frontal bossing
- Spade like hands
- Macroglossia (large tongue)
- Prognathism (large jaw)
- Excessive sweating + oily skin
- Pituitary tumour features: headaches/ bitemporal hemianopia
- Raised prolactin in 1/3 of cases - galactorrhoea
Acromegaly
Complication (4)
- HTN
- DM
- cardiomyopathy
- bowel ca
Acromegaly
Management
Surgical (2)
Medical (3)
For pituitary adenomas:
- Trans sphenoidal surgery
- Removal of ectopics
Medical 1. Pegvisomant (GH antag) 2. Somatostatin analogues - octreotide (Somatostatin is known as growth hormone inhibiting hormone) 3. Dopamine agonists
Acromegaly
What is it?
Causes (2)
Excess growth hormone production, produced in anterior pituitary gland, usually secondary to pituitary tumour
- Pituitary adenoma
- Ectopic GnRH - lung/ pancreatic ca
Explain the hypothalamic pituitary axis
Hypothalamus releases hormones than impact both anterior and posterior pituitary as follows
Hypothalamus --> Anterior pituitary CRH --> stimulates ACTH production TRH --> stimulates TSH production TRH --> stimulates prolactin GnRH --> stimulates FSH/ LH production Somatostatin --> inhibits GH production Dopamine --> inhibits prolactin production
Posterior pituitary
Oxytocin
ADH
ACTH –> adrenals –> cortisol on many tissues
TSH –> thyroid –> thyroxine
FSH/LH –> gonads –> androgen or oestrogen production
GH –> liver –> insulin growth factor release (IGF) on many tissues
Prolactin –> breast –> lactation
Oxytocin –> uterine muscle
ADH –> distal convoluting tubules –> water reabsorption
Acromegaly
Investigations (3)
- Insulin growth factor measurements
IGF-1 - MRI for pituitary tumour
- OGTT - nil response to GH in acromegaly therefore raised glucose levels, pts without acromegaly, when given OGTT their glucose levels falls to <2
Addisons
What is it?
Also known as primary adrenal insufficiency
80% of cases –> autoantibodies against adrenal cortex
Therefore reduced production of aldosterone, cortisol and androgens
Addisons
Features
- Low BP
- Hair thinning
- Weight loss
- Increased fractures
- Palmer creases hyperpigmentation
- Loss of pubic hair
- Hypoglycaemia
- Collapse/ shock/ pyrexia
Addisons
Investigations (2)
- short synACTHen/ ACTH stimulation test
Baseline cortisol measured, given synachthen and expect cortisol to double when measured at 30 minutes and 60minutes. If still low then Addison’s - 9am cortisol levels
> 500 nmol/l Addison’s very unlikely
< 100 nmol/l is definitely abnormal
100-500 nmol/l for ACTH stimulation test
Addisons
Management
- Hydrocortisone (20-30mg/day) (double if sick)
2. Fludrocortiose
How does the adrenal gland work? Include hypothalamus-pituitary axis.
Hypothalamus produces CRH CRH acts on ant. pituitary causing ACTH release ACTH acts on adrenal gland Adrenal gland split into medulla (inside) and cortex (outer). ACTH acts on cortex. Production of three hormones: 1. Mineralocorticoids e.g aldosterone 2. Glucoscorticoids e.g cortisol 3. Androgens (females mainly)
Mineralocorticoid release increase sodium reabsorption and water retention
Glucocorticoids causes:
1. Immunosuppression/ anti-inflammatory –> increased infection
2. Skin - thinning
3. Bone - increased osteoclasts, increases breakdown therefore increased risk of osteoporosis and fractures
4. Metabolic - weight gain, insulin resistance
Androgens –> increases libido
Increased mineralo/glucocorticoids and androgens has negative feedback on hypothalamus
Addisons Primary causes (7)
- Autoimmune
- TB
- HIV
- Antiphospholipid syndrome
- Meningococcal septicaemia (Waterhouse-Friderichsen syndrome)
- Metastases/ primary ca
- Congenital
Addisons
Secondary causes
Pituitary disorders: tumours/ infiltration/ irradiation
Secondary causes not associated with hyperpigmentation
Electrolyte impact of Addison's K+ Na+ Gluc Metabolic acidosis or alkalosis?
High K+, as reduced aldosterone leads to reduced Na reabsorption and therefore increased potassium retention
hyponatraemia
hypoglycaemia
Hyperkalaemic metabolic acidosis
Mx of thyrotoxicosis
MOA
Carbimazole high dose for 6 weeks/ until euthyroid then taper
Thyroid peroxidase inhibitor
Name of autoantibodies in Addison’s
anti-21-hydroxylase
Thyroid hormones sythnthesis
Thyroid made up of lobules. Lobules made up of follicles and colloid T3 T4 synthesised in the colloid. Iodide from the blood stream moves into follicle. Iodide transported to colloid Iodide uses peroxidase to create iodine
Follicle makes thyroglobulin and moves into colloid.
Thyroglobulin is made up of tyrosine
In the colide we now have tyrosine and iodine.
x1 iodine binding to tyrosine = MIT
x2 iodine binding to tyrosine = DIT
MIT+DIT = T3 DIT+DIT = T4
Name five corticosteroids in order of minimum to maximum glucocorticoid strength
Fludrocortisone
Hydrocortisone
Prednisolone
Dexamethasone + Betamethasone
Mineralocorticoid SE
Fluid retention
HTN
When do you need to taper steroids?
- > 40mg OD for 1 week
- > 3 weeks treatment
- Recently received repeat courses
Cushings syndrome Causes ACTH dependent ACTH independent Pseudo
ACTH dependent
- Pituitary adenoma = Cushing’s disease
- Ectopic ACTH production e.g lung cancer
ACTH independent
- Iatrogenic (steroids given to pt)
- Adrenal carcinoma/ adenoma
- Carney complex
Pseudo-Cushings
- ETOH excess
- Depression
Cushings
Metabolic acidosis or alkalosis
Hypokalaemic etabolic alkalosis
Cushings
Investigations (3)
- Overnight dexamethasone suppression test
- 24 hr urinary free cortisol
- CRH stimulation test
Cushings
Features
Truncal obesity Moon faces Abdominal striae Muscle wasting Amenorrhea Easy bruising Buffalo hump Fractures DM
Cushings
Explained what the overnight dexamethasone test is
Explain its results
Split into low dose and high dose dexamethasone test
10pm give 1mg dexamethasone, 9am measure cortisol and ACTH
In a pt without any issues
Give 1mg dexamethasone, this acts on hypothalamus (negative feedback) and pituitary and adrenals –> therefore in the morning, you should have a low cortisol.
If you have Cushing’s syndrome (high cortisol)
As pt is used to having lots of cortisol, haveing 1mg dexamethasone will not cause negative feedback system. Therefore cortisol level will be normal or raised.
If low dose test is suggestive of Cushing’s you will then move on to high dose.
Give 8mg of dexamethasone at 10pm
Morning measure cortisol and ACTH
If you have Cushing’s disease (pituitary adenoma), 8mg is enough to trigger negative feedback system. Therefore ACTH will decrease and cortisol will fall.
If you have an adrenal gland tumour. The adrenal gland tumour cells will produce cortisol independent of ACTH. Therefore dexamethasone will work on pituitary through negative feedback system which leads to low ACTH. However as cortisol is independent of ACTH. Cortisol levels will be raised.
If you have ectopic ACTH production. Then dexamethasone will cause reduction in CRH and therefore ACTH. However as ectopic ACTH production still going on. ACTH will be raised and thus cortisol will be raised.
To summaries
Low dose test
Low cortisol = normal
High cortisol = cushing’s syndrome
High dose test
Low ACTH and low cortisol = Cushing’s syndrome
Low ACTH and high cortisol = Adrenal carcinoma/ adenoma
High ACTH and high cortisol = ectopic
Explain CRH stimulation test
This is to determine between pituitary source or ectopic source
In a pituitary source - CRH stimulation = increased ACTH = increased cortisol
In an ectopic source - CRH stimulation = ACTH remains the same and cortisol stays the same
Mx Cushings
Pituitary source - surgery
Exogenous source - taper
Ectopic source - ketoconazole or metyrapone (adrenal steroid inhibitors)
T2DM
Diagnosis
Symptomatic can be done based on x1 result
- Fasting glucose >=7
- Random glucose/ OGTT >11 .1
- HbA1C >=48
If asymptomatic needs x2 results
T2DM
Diagnosis
Symptomatic can be done based on x1 result
- Fasting glucose >=7
- Random glucose/ OGTT at 2 hours >=11 .1
- HbA1C >=48
If asymptomatic needs x2 results
Values for diabetes
Pre diabetes
Normal
HbA1C <=41, >=48
Fasting glucose <=6, >=7
Values for diabetes
Pre diabetes/ impaired glucose tolerance
Normal
HbA1c <=41, >=48
Fasting glucose <=6, >=7
Impaired OGTT 2-hour value >= 7.8 but < 11.1
When can HbA1c not be used?
- Suspected GDM
- Children
- HIV
- CKD
- Haemaglobinopathies
- Iron deficiency anaemia untreated
- Haemolytic anaemia
T2DM treatment
Given two examples of GLP-1 mimetics
Explain how they work and how often they are given
GLP-1 mimetics e.g exenatide (BD)/ liraglutide (OD)
- works by increasing incretins
- increases insulin
- reduced glucoagon
- reduced appetite and gastric emptying
- leads to weight loss
- must be given within 1 hr to morning and evening meal SC
T2DM treatment
Give an example of DPP-4 inhibitors
Explain how they work
DPP-4 inhibitors e.g gliptins
DPP4 inhibits GLP-1, therefore inhibitors lead to increased GLP-1
HbA1c targets
How often do you check HbA1c?
Lifestyle + one medication not causing hypoglycaemia
Target = 48
Taking drugs causing hypoglycaemia
Target = 53
Every 3-6 months until stable, then 6 monthly
When do you add a second diabetic medication?
If HbA1c >=58
Medications T2DM groups (6)
- Biguanides –> metformin
- DPP4-inhibitorrs –> sitagliptin
- Sulfonylureas –> tolbutamide
- Thiazolidinediones –> pioglitazone
- SGLT-2 –> canagliflozin
- GLP-1 mimetics –> exanatide
Sulfonylureas
MOA
Adverse effects (2)
Other SE (4)
Increase pancreas insulin production
- Hypoglycaemia
- Weight gain
- Low Na
- Bone marrow suppression
- Hepatotoxicity
- Peripheral neuropathy
T2DM management
If metformin tolerated
1st line
1. Metformin
If HbA1c >58
Add
2. gliptin/ sulfonylurea/ pioglitazone/ SGLT-2
If HbA1c >58 Then combo of: metformin+sulfonylurea+ gliptin meformin+ sulfonylurea+SGLT2 metformin + sulfonylurea+ pioglitazone metformin + pioglitazone + SGLT2 insulin + metformin
If triple therapy not effective
metformin + sulfonylurea + GLP-1 mimetic
T2DM management
If metformin not toelrated (3)
1st line
1. Gliptin/ sulfonylurea/ pioglitazone
If HbA1c >58
2. Combo of any of the above two
If HbA1c >58
3. Insulin + metformin
When would you give GLP-1 mimetics?
BMI >=35 European and high weight OR
BMI <35 and unable to use insulin or weight loss would benefit other comorbidities
T1DM Target HbA1c How often should it be checked How often should they check their glucose level? What should the levels be?
Target 48
Check every 3-6 months
Check four times a day, before every meal, before bed
4-7 before meals
5-7 fasting glucose/ on waking
Sick day rules for T1DM
Do not omit insulin
Check glucose levels every 1-2 hours including the night
T1DM insulin regime of choice
When would you add metformin?
Multiple basal-bolus regimens over mixed insulins
1st line
BD insulin detemir
2nd line
OD insulin glargine or detemir
BMI >25 add metformin
What is Charcot’s arthropathy?
Joint dislocations secondary to peripheral neuropathy
How often should patient’s be screened for diabetic foot disease?
How is it done?
Annual basis
To screen for ischaemia:
1. Palpate dorsalis pedis and post tibial artery
To screen for neuropathy:
2. 10g monofilament on various parts of the sole of the foot
Diabetic foot disease
Low risk
Moderate risk
High risk
Low risk: No RF, just a callus
Mod risk: deformity/ neuropathy/ non-critical limb ischaemia
High risk: prev amputation/ ulceration on RRT/ combination of above two RF
What is metabolic syndrome?
Central obesity AND At least x2 of: - raised BP - impaired glucose tolerance - high cholesterol
How often should diabetic patients be checked for retinopathy?
At diagnosis and annually thereafter
What are the most common precipitating factors for DKA? (2)
- MI
2. Missed insulin doses
DKA
Features
- AP
- polyuria, polydipsia, dehydration
- Kussmaul respiration (deep hyperventilation)
- Acetone-smelling breath (‘pear drops’ smell)
DKA
Diagnostic criteria
- glucose > 11 or known DM
- pH < 7.3
- bicarb < 15
- ketones > 3 or urine ketones ++ on dipstick
DKA Mx
- Isotonic saline
- IV insulin infusion 0.1unit/kg/hour, once glucose <15 start 5% dex
- Correct hypokalaemia secondary to insulin
- Continue long acting insulin, stop short acting insulin
(0.9% normal saline over 1 hr for first bag, second + third bag over 2 hours NaCl with potassium chloride, fourth + fifth bag over 4 hours NaCl with potassium chloride)
At what value of K+ do you need to replace it?
3.5-5.5 give 40mmols
What are young adults/ children at risk of developing if we give fluids at too fast a rate during a DKA
Cerebral oedema - headache, irritability, visual disturbance –> usually occurs 4-12 hrs post rx
What can cause a falsely low HbA1c?
Sickle-cell anaemia
GP6D deficiency
Hereditary spherocytosis
What can cause a falsely high HbA1c?
Vitamin B12/folic acid deficiency
Iron-deficiency anaemia
Splenectomy
HHS
Features
Occurs over a few days
- Dehydration + hyperviscosity of blood
- Polyuria
- Fatigue/ lethargy/ N&V
- Altered conscious level
HHS
Diagnostic criteria
- Hypovolaemia
- High glucose >30 without significant ketonaemia or acidosis
- Raised serum osmolarity > 320
HHS
Mx
How often do you need to check osmolality?
Estimated fluid loss
- NaCl 0.9%
If not bringing down osmolality switch to NaCl 0.45%
Check osmolality hourly
Estimated loss 100 - 220 ml/kg
Replace 50% of fluid loss in 12 hours, then further 50% in next 12 hours.
HHS
Target glucose level
10-15
When would you start insulin in HHS?
What rate?
Do not start insulin in T2DM unless ketones are present
Dose would be fixed rate 0.05 units/kg/hr
What is Grave’s disease?
Name the antibodies (2)
Autoimmune antibodies leading to hyperthyroidism
- TSH receptor stimulating antibodies
- anti-TPO autoantibodies
Grave’s disease
Features (4)
- exophthalmos
- ophthalmoplegia
- pretibial myxoedema
- thyroid acropachy (clubbing, soft tissue swelling of hands and feet and periosteal new bone formation)
Grave’s disease
Mx
- Carbimazole until euthyroid 40mg - 12-18 months
OR - Carbimazole until euthyroid, then add thyroxine - 6-9 months
Contraindications for Grave’s
- Pregnancy
2. <16 yo
Causes of gynaecomastia
- Kallman’s + Klinefelters
- Mumps
- Liver disease
- Testicular cancer (seminoma secreting HCG)
- hyperthyroidism
- haemodialysis
Hashimoto’s
What is it?
Antibodies (2)
Autoimmune condition causing hypothyroidism
- anti-thyroid peroxidase (TPO)
- anti-thyroglobulin (Tg) antibodies
Hypothyroidism
Primary causes: (6)
Secondary causes:
- Hashimoto’s
- Subacute thryroiditis (de Quervain’s)
- Riedel thyroiditis
- Iodine deficiency
- Drugs e.g carbimazole, amiodarone, lithium
- Post thyroidectomy
Hypothyroidism is associated with which four conditions?
- T1DM
- MALT lymphoma
- Pernicious anaemia
- Addison’s
Causes of hyperthyroidism (2)
- Grave’s
2. Toxic multinodular goitre
Physiology of parathyroid gland
What is the purpose of vit D?
Low calcium leads to increase in PTH
Role of PTH is to increase calcium levels
PTH causes:
1. Increased gut absorption
2. Increased reabsorption of calcium from the kidneys
3. Increased osteoclast activity, to break down bone to increase calcium levels
Vit D does the same as PTH, increase PTH leads to increase conversion of vit D into active form so it can help with above effects.
Explain primary hyperparathyroidism
High PTH
High calcium
Low phosphate
Caused by parathyroid glad tumour
Explain secondary hyperparathyroidism
High PTH
Low calcium
High phosphate
Caused by vit D deficiency or CKD
Explain tertiary hyperparathyroidism
High PTH
High calcium
Low phosphate
Secondary to hyperplasia of parathyroid gland due to secondary hyperparathyroidism after it has been corrected
Hypoparathyroid disease
What is it?
Usually caused by?
Mx
Low PTH and therefore low calcium and high phosphate
Usually secondary to thyroidectomy
Mx alfacalcidol
Hypoparathyroidism symptoms (Hint: same as hypocalcaemia)
- Trousseau’s sign
- Chvostek’s sign
- Muscle spasm
- Perioral paraesthesia
ECG prolonged QT
What is pseudohypoparathyroidism?
Low calcium, high PTH, high phosphate
Secondary to target cells being insensitive to PTH
Abnormality in a G protein
Features of pseudohypoparathyroidism
- Short stature
- Low IQ
- Short 4th and 5th metacarpals
Lack of smell (anosmia) in a boy with delayed puberty = ?
Kallman’s syndrome
When would meglitinides be used?
How do they work?
SE (2)
Used in pt’s with DM with erratic lifestyles
Increased pancreatic insulin secretions
Similar to sulfonylureas
Cause weight gain and hypoglycaemia (but less so than sulfonylureas)
MEN Type I
Features
Which gene?
3Ps 1. Pituitary 2. Parathyroid gland 3. Pancreas MEN 1 gene on chrm 11
Features
Hypercalcaemia
Moans boans abdominal groan and psychic moans
MEN Type IIa
Which gene?
2Ps
Medullary thyroid cancer
1. Parathyroid gland
2. Phaeo
RET oncogene
MEN Type IIb
Which gene?
1P Medullary thyroid cancer Marfanoid body habitus 1. Phaeo \+ Neuromas
RET oncogene
Phaeochromocytoma
What is it?
Name three associated conditions
Catecholamine secreting tumour
- MEN Type 2
- Neurofibromatosis
- von Hippel-Lindau syndrome
Phaeochromocytoma
Investigation
Mx
- 24 hr urinary collection of metanephrines
Mx
- Stabilise HTN with:
- first line: alpha blocker e.g phenoxybenzamine
- second line: beta blocker e.g propranolol - Surgery
What is Conn’s syndrome?
Primary hyperaldosteronism secondary to adrenal adenoma
Causes increased water and sodium reabsorption
Leading to HTN and hypokalaemia and an alkalosis
Most common cause of primary hyperaldosteronism?
Bilateral adrenal hyperplasia
Leading to increase aldosterone production
Leading to increased water and sodium reabsorption
Leading to HTN and hypokalaemia and an alkalosis
Features of primary hyperaldosteronism
- HTN
2 Hypokalaemia - Alkalosis
Primary hyperaldosteronism
Ix (3)
- Plasma aldosterone/renin ratio
- High-resolution CT abdomen
- Adrenal vein sampling
What would the plasma aldosterone/renin ratio show in primary hyperaldosteronism ?
High aldosterone levels alongside low renin levels (due to negative feedback)
Why is a high-resolution CT abdomen used primary hyperaldosteronism?
Used to differentiate between unilateral and bilateral sources of aldosterone excess
Why is adrenal vein sampling used in primary hyperaldosteronism?
To identify the gland secreting excess hormone in primary hyperaldosteronism
Mx
Adrenal adenoma (1)
Bilateral adrenocortical hyperplasia (1)
- Surgery
2. Aldosterone antagonists (spiro)
Primary hyperparathyroidism
Features
(Hint: same as hypercalcaemia)
- Osteoporosis/ osteomalacia/ fracture
- Renal stones and diabetes insipidus (polyuria and polydipsia)
- Constipation/ N&V/ peptic ulceration/ pancreatitis
- Psychosis/ memory issues/ depression
- Corneal calcification
- HTN
Primary hyperparathyroidism
Ix
- High calcium, low phosphate, high PTH
2. technetium-MIBI subtraction scan
Primary hyperparathyroidism
Mx
Mx
1. parathyroidectomy
If >50yo and calcium level less than 0.25 above normal level and no organ end damage:
1. Conservative management such as cinacalcet
Features of excess prolactin in
- Men (3)
- Women (4)
M: reduced libido, galactorrhea, impotence
F: amenorrhea, galactorrhea, infertility, osteoporosis
Cause of raised prolactin (5)
- Acromegaly
- Pregnancy
- Prolactinoma
- Stress
- Primary hypothyroidism (as TRH stimulates prolactin)
- PCOS
Pepperpot skull on xray is characteristic of which condition?
Primary hyperparathyroidism
What is the classification of pituitary adenomas
Micro <1cm Macro >1cm OR Secretory - produces hormones to excess Non secretory - does not produce hormones to excess
What is the most common form of pituitary adenoma?
Prolactinomas
Diagnostic investigation for prolactinoma
Mx
- MRI
Mx
- DA e.g cabergoline/ bromocriptine
- Surgery if fails to respond to medical therapy
What is Riedel’s thyroiditis?
What is it associated with?
Dense fibrous tissue replaces normal thyroid tissue causing hypothyroidism
Retroperitoneal fibrosis
1. hard, fixed, painless goitre
What is sick euthyroid syndrome?
What will you find on bloods?
Mx
AKA non thyroidal illness
TSH, thyroxine and T3 are all low
Sometimes TSH can be normal (inappropriately normal given low thyroxine and T3)
Mx - nil, normally recovers post ilness
Subacute (De Quervain’s) thyroiditis
Presents with hyperthyroidism following a viral infection but is actually hypothyroidism.
Subacute (De Quervain’s) thyroiditis
Explain the four phases
phase 1 (lasts 3-6 weeks): hyperthyroidism, painful goitre, raised ESR phase 2 (1-3 weeks): euthyroid phase 3 (weeks - months): hypothyroidism phase 4: thyroid structure and function goes back to normal
Subacute (De Quervain’s) thyroiditis
Ix
Mx
thyroid scintigraphy: globally reduced uptake of iodine-131
Mx
- Self limiting
- NSAIDs/ aspirin for pain
- Steroids in severe cases
Subclinical hypothyroidism
Bloods
Mx
TSH raised but T3, T4 normal Mx TSH is between 4 - 10 If asymptomatic - repeat bloods 6 months <65yo and symptomatic --> trial levothyroxine If older - watch and wait approach
TSH>10
=<70yo = start rx
Otherwise watch and wait
Toxic multinodular goitre
What is it?
thyroid nodules that secrete excess thyroid hormones
What is the Ferriman-Gallwey scoring system used in?
Gold standard scoring system for assessment of hirsutism
Mx of hirsutism (2)
Mx of facial hirsutism (1)
- Weight loss
- COCP
Facial hirsutism - Topical eflornithine (should start seeing results 6-8 weeks)
- if no improvement after 4 months, refer to endocrine
Hypothyroidism Mx
In pregnancy Mx
If >50yo or IHD or severe hypothyroidism start with a low dose e.g 25mcg
Otherwise start on 50-100mcg
Recheck TFTs 2-3 months and titrate until TSH normalised.
Pregnancy - increase dose by 25-50mcg
Impaired glucose tolerance definition
Impaired fasting glucose =
fasting glucose <7
OGTT/ random 7.8-11.1
Impaired fasting glucose = fasting gluc 6.1-7.0
Papillary thyroid cancer - bloods
Nil changed to TFTs as they do not secrete thyroxine