Passmed Endocrinology Mushkies Flashcards
What is the pathophysiology of DKA?
DKA is causes by uncontrolled lipolysis which results in an excess of free fatty acids that are ultimately converted into ketone bodies
What are the 3 most common precipitating factors of DKA?
- Infection
- Missed insulin doses
- MI
What are some features of DKA?
- Abdo pain
- Polyuria, polydipsia, dehydration
- Kussmaul respiration (deep hyperventilation)
- Acetone-smelling breath (pear-drops smell)
What are the diagnostic criteria for DKA?
- Glucose >11mmol/l or known DM
- Ketones > 3mmol/l or ++ on dipstick
- pH < 7.3
4, Bicarb < 15mmol/l
What is the management of DKA?
- 0.9% saline
- Insulin = 0.1 unit/kg/hour
- 5% dextrose once blood glucose < 15mmol/l
- Correction of hypokalaemia
- Long acting insulin continued, short acting insulin stopped
How fluid depleted are most pts with DKA?
5-8 litres
What is the JBDS fluid replacement regime for pts with DKA with SBP>90mmHg?
- 0.9% NaCL = 1000ml over 1st hour
- 0.9% NaCL + KCl = 1000ml over next 2hrs
- 0.9% NaCL = 1000ml over next 2hrs
- 0.9% NaCL = 1000ml over next 4hrs
- 0.9% NaCL = 1000ml over next 4hrs
- 0.9% NaCL = 1000ml over next 6 hours
What is the JBDS potassium replacement guideline for pts in DKA?
Potassium level in 1st 24 hours
- > 5.5 = No K
- 3.5-5.5 = 40 mmol/L
- <3.5 = senior review as additional K needs to be given
What are some complications of DKA and its management?
GVAAAI
- Gastric stasis
- VTE
- Arrhythmias secondary to hyperkalaemia/iatrogenic hypokalaemia
- ARDS
- AKI
- Iatrogenic due to incorrect fluid therapy = cerebral oedema, hypokalaemia, hypoglycaemia
What are children/young adults particularly susceptible during fluid resus for DKA?
- Cerebral oedema, usually 4-12 hours after commencement of tx
- 1:1 nursing ut monitor neuro obs, headache, irritability, visual disturbance, focal neurology etc.
- Any suspicion of oedema –> CT head and senior review
What does an ‘unrecordable’ blood glucose mean?
It is rather high
For group 1 vehicles, when are diabetic pts on insulin allowed to drive?
- If they have hypoglycaemic awareness
- Not more than one episode of hypoglycaemia requiring the assistance of another person within the preceding 12 months
- No relevant visual impairment
What overdose could cause metabolic acidosis with a raised anion gap?
Aspirin
What is the eponymous triad for an insulinoma?
Whipple’s triad
What is Whipple’s triad of symptoms for an insulinoma?
- Hypoglycaemia with fasting or exercise
- Reversal of symptoms with glucose
- Recorded low BMs at the time of symptoms
What is an insulinoma?
A neuroendocrine tumour deriving mainly from the pancreatic Islets of Langerhans cells
What are some stats about insulinomas?
- Most common pancreatic endocrine tumour
- 10% malignant
- 10% multiple
- Of pts with multiple tumours, 50% have MEN1
What are the features of MEN1?
3 Ps
- Pituitary adenoma
- Parathyroid hyperplasia
- Pancreatic tumour e.g. insulinoma, gastrinoma (recurrent peptic ulceration)
How is an insulinoma diagnosed?
- Supervised, prolonged fasting (up to 72 hours)
2. CT pancreas
What is the management for an insulinoma?
- Surgery
2. Diazoxide and somatostatin if pts are not candidates for surgery
What are features of MEN2A?
- Parathyroid hyperplasia
- Medullary Thyroid Carcinoma
- Phaeochromocytoma
What are features of MEN2B?
- Mucosal neuromas
- Marfanoid body habitus
- Medullary Thyroid Carcinoma
- Phaeochromocytoma
What is the management of subclinical hypothyroidism in the elderly?
Watch and wait
What are the TFT features of subclinical hypothyroidism?
- Raised TSH
- Normal T3 and T4
- No symptoms
What is the risk of progression to overt hypothyroidism from subclinical hypothyroidism?
2-5% per year
Pt <65 y/o with symptoms of hypothyroidism, high TSH, normal T3 and T4?
Trial of levothyroxine, if there is no sx improvement, stop
Mx of asymptomatic subclinical hypothyroidism <65 y/o?
Observe are repeat TFTs in 6m
TSH > 10 and normal T3 and T4 management?
Start tx even if asymptomatic
What is the management of myxoedema coma?
Levothyroxine and hydrocortisone
Why is hydrocotisone given for myxoedema coma?
To treat adrenal insufficiency, pts w/ myxoedema due to secondary hypothyroidism are at risk of hypopituitarism due to location of lesion, thus are treated as presumed adrenal insufficiency until it has been ruled out
How can you classify the features of hypothyroidism?
- General = weight gain, lethargy, cold intolerance
- Skin = dry, cold, non-pitting oedema, coarse hair, loss of lateral 1/3rd of eyebrow
- GI = constipation
- Gynae = HMB
- Neuro = dereased deep tenon reflexes, carpa tunnel syndrome
- Hoarse voice
What mutation accounts for 70% of MODY cases?
Hepatic Nuclear Factor 1 Alpha (HNF1A) mutation (MODY 3)
What is the optimal treatment for HNF1A-MODY?
Sulfonylureas
What is MODY?
The development of T2DM in pts <25y/o, typically inherited in an autosomal dominant fashion
How many different mutations are documented to cause MODY?
6
What malignancy is MODY 3 associated with?
HCC
How do you diagnose T2DM in a symptomatic pt?
- Fasting glucose ≥ 7.0 mmol/l OR
- Random glucose ≥ 11.1 mmol/l OR
- Post OGTT glucose ≥ 11.1mmol/l
How do you diagnose T2DM in an asymptomatic pt?
Same as symptomatic, but must be demonstrated on 2 separate occasions
What is the HbA1c T2DM diagnostic threshold?
> 48mmol/mol (6.5%)
What is pre-diabetes, in terms of both HbA1c and fasting glucose?
- HbA1c 42-47 mmol/l (6.0-6.4%)
2. Fasting glucose 6.1-6.9 mmol/l
What is normal fasting glucose in terms of both HbA1c and fasting glucose?
- HbA1c < 41mmol/mol (5.9%)
2. Fasting glucoe <6.0mmol/l
What is 48mmol/mol HbA1c in %?
6.5%
What is 41mmol/mol HbA1c in %?
5.9%
Does a HbAlc value of less than 48 mmol/mol (6.5%) exclude diabetes?
No, fasting samples are more sensitive
What can cause misleading HbA1c results?
Conditions that cause increased red cell turnover
- Haemoglobinopathies
- Haemolytic anaemia
- Untreated IDA
- Children
- HIV
- CKD
- Steroids
What defines impaired fasting glucose?
6.1-6/9 mmol/l
What defines impaired glucose tolerance?
- Fasting plasma glucose <7.0mmol/l
2. OGTT > 7.8 but less than 11.1 mmol/l
What should pts with IFG be offered?
An OGTT to rule out a diagnosis of diabetes
What is the first line investigation for Conn’s syndrome?
Renin:aldosterone ratio
What are 3 causes of primary hyperaldosteronism?
- Bilateral idiopathic adrenal hyperplasia (70%)
- Conn’s syndrome (adrenal adenoma)
- Adrenal carcinoma
What are 4 features of primary hyperaldosteronism?
- Hypertension
- Hypokalaemia
- Hypernatraemia
- Alkalosis
What is the management of bilateral idiopathic adrenal hyperplasia?
Aldosterone antagonist e.g. spironolactone
What is the management of Conn’s syndrome?
Surgery
What are the different types of thyroid cancers?
- Papillary (65%)
- Follicular (20%)
- Medulllary (5%)
- Anaplastic (1%)
- Lymphoma
Where does papillary thyroid cancer commonly metastasise to?
Cervical lymph nodes
What is a tumour marker for papillary and follicular thyroid carcinoma?
Thyroglobulin
What do you see on light microscopy of papillar thyroid carcinoma?
Orphan Annie eyes
Where does follicular thyroid carcinoma commonly metastasise to?
Lung and bones
Where do MTCs originate from and as such what is the tumour marker?
Parafollicular Cells, that produce Calcitonin
What demographic does papillary thyroid cancer usually affect, and what is its prognosis?
Young females, excellent prognosis
What condition is thyroid lymphoma associated with?
Hashimoto’s thyroiditis
What is the management of papillary and follicular thyroid cancer?
- Total thyroidectomy
- Followed by radioiodine (I-131) to kill residual cells
- Yearly thyroglobulin levels to detect early recurrent disease
In what demographic is anaplastic thyroid carcinoma most common?
Elderly females
What steroid has minimal glucocorticoid activity, and very high mineralocorticoid activity?
Fludrocortisone
What steroid has high glucocorticoid activity, and high mineralocorticoid activity?
Hydrocortisone
What steroid has high glucocorticoid activity, and low mineralocorticoid activity?
Prednisolone
What steroids have very high glucocorticoid activity, and minimal mineralocorticoid activity?
- Dexamethasone
2. Betamethasone
What are the s/es of
mineralocorticoids?
Fluid retention and hypertension
What are the s/es glucocorticoids?
- Endocrine = Cushings
- MSK = osteoporosis, proximal myopathy, AVN femoral head
- Immune = suppression
- Psych = Insomnia, mania, depression, psychosis
5.
How does Kartagener’s syndrome present?
Dextrocardia and a history of recurrent sinusitis/bronchitis
What is the karyotype of Klinefelters?
47XXY
What are some features of klinefelter’s?
- Taller than average
2, Lack of secondary sexual characteristics - Small, firm testes
- Infertile
- Gynaecomastia
- Elevated gonadotrophin levels but low testosterone
What diabetes drug is c/i in HF?
Thiazolidinediones e.g. pioglitazone, as they cause fluid retention
What is the MOA of thiazolidinediones?
- PPAR-y agonists in adipocytes to promote adipogenesis and fatty acid uptake
- Reduce peripheral insulin resistance
What are some features of Hashimoto’s thyroiditis?
1, Hypothyroidism
- Firm, non-tender goitre
- Anti-TPO Abs (also anti-Tg Abs)
How much more common is hashimoto’s thyroiditis in women?
10x
High TSH, normal T4, on levothyroxine, whats going on?
Poor compliance with medication - started taking thyroxine properly just before test. This will correct the thyroxine level but the TSH takes longer to normalise
What is Nelson’s syndrome?
Rapid enlargement of an ACTH producing adenoma that occurs after bilateral adrenelectomy for Cushings syndrome
What is the prevalence of pituitary adenomas?
10% all people
How can pituitary adenomas be classified?
- Size (microadenoma <1cm, macroadenoma >1cm)
2. Hormonal status (functioning vs. non-functioning)
What is the most common pituitary adenoma?
Prolactinoma
How do pituitary adenomas cause symptoms?
- Excess hormone production
- Depletion of hormone due to compression of normal functioning gland
- Headache due to stretching of dura within/around pituitary fossa
- Bitemporal hemianopia due to compression of optic chiasm
What are the components of a pituitary blood profile?
- GH
- Prolactin
- ACTH
- LH
- FSH
- TFTs
What are some differentials of a pituitary adenoma?
- Pituitary hyperplasia
- Craniopharyngioma
- Meningioma
- Brain mets
- Lymphoma
- Hypophysitis
- Vascular malformation e.g. aneurysm
What are the general management strategies for pituitary adenomas?
- Hormonal therapy
- Surgery (e.g. transsphenoidal transnasal hypophysectomy)
- Radiotherapy
What are the TFT findings of sick euthyroid syndrome?
Everything is low (sometimes TSH is normal)
What 2 conditions account for 90% of cases of hypercalcaemia?
- Primary hyperparathyroidism (commonest in non-hospitalised pts)
- Malignancy (commonest in hospitalised pts)
What are some malignancies that cause hypercalcaemia?
- Bone mets
- Myeloma
- PTHrP from squamous cell lung cancer
What are some ‘other’ causes of hypercalcaemia
- Endo = Acromegaly, Thyrotoxicosis, Addison’s, Vit D intoxication
- Inflammation = sarcoidosis
- Drugs = thiazides
- Dehydration
- Milk-alkali syndrome
How many phases are there in subacute thyroditis?
4 phases following viral infection
What are the phases of subacute thyroiditis?
- 3-6 weeks = hyperthyoidism, painful goitre, raised ESR
- 1-2 weeks = euthyroid
- Wks-ms = hypothyroidism
4 . Thyroid structure and function returns to normal
What investigation can you do for subacute thyroiditis?
Thyroid scintigraphy –> globally reduced uptake of Iodine-131
What is the management of subacute thyroiditis?
- Usually self limiting, no tx
- Thyroid pain may respond to aspirin or NSAIDs
- If hypothyroidism develops –> steroids
What are the causes of primary hypothyroidism?
- AI (Hashimoto’s, atrophic)
- Iodine deficiency
- Thyroiditis (post-viral, post-partum, Riedel’s)
- Iatrogenic (thyroidectomy, radioiodine, drugs)
What is the triad of presentation of phaeos?
- Sweating
- Headaches
- Palpitations
What is the first line investigation for phaeos?
24hr Urinary metanephrines (97% sensitivity)
What are the 3 genetic associations of phaeos?
- MEN II
- vHL
- NF
What is the rule of 10%s for phaeos?
- 10% extra-adrenal
- 10% bilateral
- 10% familial
- 10% children
- 10% malignant
- Discussed 10x more than it is actually seen
What is the most common extra-adrenal site for phaeos?
The organ of Zuckerkandl, adjacent to the bifurcation of the aorta
What is the management of phaeos?
- Alpha blocker (e.g. phenoxybenzamine) THEN
- Beta blocker (e.g. propranolol) THEN
- Surgery
What are the causes of primary hyperparathyroidism?
- Solitary adenoma (80%)
- Hyperplasia (15%)
- Multiple adenomas (4%)
- Carcinoma (1%)
What are the features of primary hyperparathyroism
‘Bones, stones, abdominal groans and psychic moans’
1. Bone pain/fracture
2. Renal stones, polydipsia, polyuria
3. Peptic ulceration/constipation/pancreatitis
4. Depression
5, HTN
What is a characteristic X ray finding of primary HPT?
Pepperpot skull
What scan can be done for primary HPT?
Technetium-MIBI subtraction scan
What is the management of primary HPT
- Definitive = total parathyroidectomy
- Conservative management if there is no evidence of end organ damage and and calcium levels arent too high
- Calcimimetic agents e.g. cinacalcet in pts unsuitable for surgery
What are some causes of an Addisonian crisis?
1, Sepsis or surgery causing acute exacerbation of chronic insufficiency
- Adrenal haemorrhage (Waterhouse-Friderichsen syndrome due to fulminant meningococcaemia)
- Steroid withdrawal
What is the management of an Addisonian crisis?
- Hydrocortisone 100mg IM/IV
- 1L normal saline infused over 30-60mins or with dextrose if hypoglycaemic
- Continue hydrocortisone 6 hrly until pt is stable (no fludrocortisone required as hydrocortisone exerts weak mineralocorticoid action)
What is the tx for painful diabetic neuropathy to relieve pain?
- First line = Duloxetine, Amitryptiline, Gabapentin, Pregabalin
- If 1st drug doesnt work try one of the others
- Tramadol may be used as rescue therapy for acut exacerbations
- Topical capsaicin for localised neuropathic pain e.g. post-herpetic neuralgia
- Pain clinics
How can diabetes cause GI symptoms?
GI autonomic neuropathy
What are 3 forms of GI autonomic neuropathy?
- Gastroparesis
- Chronic diarrhoea (often at night)
- GORD (caused by decreased lower oesophageal pressure)
What are the symptoms and management for gastroparesis due to GI autonomic neuropathy?
- Sx = erratic blood glucose control, bloating and vomiting
2. Mx = metoclopramide, domperionde, erythromycin (prokinetic agents)
Thyrotoxicosis with tender goitre?
Subacute (De Quervain’s) thyroiditis
What is the infusion rate of insulin during DKA?
0.1 unit/kg/hr
What is the most common cause of thyrotoxicosis?
Graves’ disease
What are features seen in Graves that arent seen in other causes of thyrotoxicosis
- Eye signs (30%) pts = exophthalmos, ophthalmoplegia
- Pretibial myoxoedema
- Thyroid acropachy
What Abs are seen in Graves disease?
- TSH receptor stimulating Abs (90%)
2. Anti-thyroid peroxidase Abs (75%)
In whom does a hyperosmolar hyperglycaemic state commonly present?
In the elderly with T2DM
What has higher mortality, HHS or DKA?
HHS
What are some salient vascular complications of HHS?
- MI
- Stroke
- Peripheral arterial thrombosis
How long does it take for DKA and HHS to onset?
- DKA = hours
2. HHS = days
What is the pathophysiology of HHS?
- Hyperglycaemia –> osmotic diuresis w/ associated loss of sodium and potassium
- Severe volume depletion –> very high serum osmolality (typically >320 mosmol/kg) –> hyperviscosity of blood
What are some clinical features of HHS?
- General - fatigue, lethargy, N&V
- Neuro = altered consciousness, headaches, papilloedema, weakness
- Haem = hyperviscosity –> MI, stroke, peripheral arterial thrombosis
- CVS = dehydration, hypotension, tachycardia
How is HHS diagnosed?
- Hypovolaemia
- Marked hyperglycaemia (>30mmol/l) WITHOUT significant ketonaemia or acidosis
- Markedly raised serum osmolality (>320 mosmol/kg)
What are the goals of management of HHS?
- Normalise osmolality (gradually)
- Replace fluid and e- loss
- Normal blood glucose (gradually)
What are fluid losses in HHS estimated to be?
100-220ml/kg
What is the fluid replacement for HHS?
- 0.9% Nal, rate of rehydration determined by clinical picture
- 0.45% NaCl if serum osmolality is not declining with normal saline
What is the goal of fluid replacement in initial management of HHS?
Replace 50% loss in first 12 hours, remainder in next 12 hours, but use your clinical judgement
What should be carefully monitored during tx of HHS?
Serum osmolality, glucose and sodium. Should be plotted on a graph initially.
What are the ideal rates of fall of sodium and glucose during management of HHS?
- Na = Should not exceed 10mmol/l in 24hrs
2. Glucose = 4-6mmol/hr, targeting a blood glucose b/w 10-15mmol/l
Should insulin usually be used for management of HHS, and explain?
- NO
- Fluid replacement alone with 0.9% sodium chloride solution will result in a gradual decline of blood glucose and osmolarity
- Because most patients with HHS are insulin sensitive (e.g. it usually occurs in T2DM), administration of insulin can result in a rapid decline of serum glucose and thus osmolarity, and may precipitate CPM
Why are potassium levels not as concerning in HHS?
Pts with HHS are potassium deplete but less acidotic than those with DKA so potassium shifts are less pronounced. K should be replaced or omitted as required during management
How many units of insulin are in 1ml of standard insulin?
100 units
How can you classify insulin?
- By manufacturing process
2. By duration of action
What are the different manufactured forms of insulin
- Porcine = from pig pancreas
- Human sequence = enzyme modification of porcine or from recombinant DNA or yeast
- Analogues
What are the different subtypes of insulin based on duration of action?
- Rapid acting analogues
- Short acting
- Intermediate acting
- Long acting analogues
- Premixed preparations
What is the onset, peak and duration of rapid acting insulin?
O = 5 mins P = 1 hour D = 3-5 hours
What is the onset, peak and duration of short acting insulin?
O = 30 mins P = 3 hours D = 6-8 hours
What is the onset, peak and duration of intermediate acting insulin?
O = 2 hours P = 5-8 hours D = 12-18 hours
What is the onset, peak and duration of long acting insulin?
O = 1-2 hours P = flat profile D = up to 24 hours
What are some rapid acting insulin analogues?
- Insulin aspart = NovoRapid
2. Insulin lispro = Humalog
What are some short acting insulins?
- Actrapid (soluble)
2. Humulin (soluble)
What are some intermediate acting insulins?
Isophane insulin, often used in premixed formulation with long acting insulin
What are some long acting insulins?
- Insulin detemir = Levemir = Od or BD
2. Insulin glargine = Lantus = OD
What is a premixed insulin preparation?
- Combine intermediate acting insulin with with either:
- Rapid acting insulin analogue OR
- Soluble insulin
Why is it important to rotate insulin injection sites?
To prevent lipdystrophy
What menstrual problem is hyperthyrodism associated with?
Oligomenorrhoea or amenorrhoea
What menstrual problem is hypothyroidism associated with?
Menorrhagia
How can hypothyroidism be classified?
- Primary = problem with gland itself
- Secondary = disorder of pituitary gland or lesion pressing on it
- Tertiary = disorder of hypothalamus
- Congenital = problem with thyroid dysgenesis or dyshormonogenesis
What drugs can cause hypothyroidism?
Lithium and amiodarone
What is Riedel’s thyroiditis?
Hypothyroidism caused by fibrous tissue replacing the normal thyroid parenchyma, causing a painless goitre
What is the most common cause of hypothyroidism in the developed world?
Hashimoto’s thyroidits
What is the most common cause of hypothyroidism in the developing world?
Iodine deficiency
What drug can cause both hypo and hyperthyroidism?
Amiodarone
What is a good way to classify the features of hypo/hyperthyroidism?
GGG CNS
- General
- GI
- Gynae
- Cardiac
- Neuro
- Skin
How can you classify the features of thyrotoxicosis?
- General = Weight loss, restlessness, heat intolerance
- GI = diarrhoea
- Gynae = a/oligomenorrhoea
- Cardio = palpitations
- Neuro = anxiety, tremor
- Skin = sweating, pretibial myxoedema, thyroid acropachy
What component of TFTs is used to guide treatment and why?
TSH, as it is the most sensitive marker of thyroid disease
What are some treatments for thyrotoxicosis?
- Cause = carbimazole, radioiodine
2. Complications = propranolol
What is the MOA of carbimazole?
Blocks TPO from coupling and iodinating the tyrosine residues on thyroglobulin –> reduced thyroid hormone production
What is the most salient s/e of carbimazole?
Agranulocytosis
When should a second drug be added in T2DM?
If HbA1c is > 58mmol/l
What is the target HbA1c for pts being managed with lifestyle, diet and 1 drug not associated with hypoglycaemia?
48mmol/mol
What is the target HbA1c for pts on any drug associated with hypoglycaemia?
53mmol/mol
How often should HbA1c be checked in pts with diabetes?
Every 3-6 months until stable and then every 6 months
How does NICE split the diabetes treatment pathways?
Depending on if they can tolerate metformin or not
What is the pathway for treatment of a pt who can tolerate metformin?
- Metformin –> HbA1c > 58mmol/mol –>
- Metformin + sulfonylurea/pioglitazone/gliptin/SGLT2-inhibitor –> HbA1c > 58mmol/mol –>
- Metformin + 2 others (triple therapy) –> not effective/tolerated/contraindicated AND BMI >35 –>
- Metformin + sulfonylurea + GLP1 mimetic
- Insulin
What is the pathway for treatment of a pt who can’t tolerate metformin?
- Sulfonylurea/gliptin/pioglitazone –> HbA1c>58mmol/mol
- Combine 2 of them –> HbA1c>58mmol/mol
- Insulin
What is HbA1c 58mmol/mol as a %?
7.5%
What is first line statin for those with QRISK score > 10%?
Atorvastatin 20mg OD (primary prevention dose)
What is the secondary prevention dose of statin?
Atorvastatin 80mg OD
Why does diabetic foot disease occur?
- Neuropathy = loss of protective sensation, Charcot’s arthropathy, dry skin
- Peripheral arterial disease = micro and macrovascular ischaemia
What are some complications of diabetic foot disease?
- Calluses
- Ulcers
- Charcot’s arthropathy
- Cellulitis
- Osteomyelitis
- gangrene
How does diabetic foot disease present?
- Neuropathy
- Ischaemia = absent foot pulses, reduced ABPI, intermittent claudication
- Complications
How can you screen for diabetic foot disease?
- Ischaemia = Dorsalis pedis and posterior tibial artery palpation
- Neuropathy = 10g monofilament on various parts on sole of the foot
Does any vision change in thyroid eye disease require urgent review by a specialist?
Yes
What percentage of pts with Graves have thyroid eye disease?
25-50%
What is the pathophysiology of thyroid eye disease?
AI response against TSH receptor –> retro-orbital inflammation –> GAG and collagen in the muscles
What is the most important modifiable RF for the development of thyroid eye disease?
Smoking
What treatment may increase the inflammatory sx seen in thyroid eye disease?
Radioiodine tx
What are some features of thyroid eye disease?
- Exophthalmos
- Ophthalmoplegia
- Conjunctival oedema
- Optic disc swelling
- Inability to close eyelids –> dry, sore eyes
What is the management of thyroid eye disease?
- Topical lubricants to prevent corneal inflammation caused by exposure
- Steroids
- Radiotherapy
- Surgery
What could cause eye suddenly popping out with thyroid eye disease?
Globe subluxation
Most common cause of Addisons in UK?
AI
Most common cause of Addisons worldwide?
TB
What is Addison’s disease?
Primary adrenal insufficiency
What are some features of Addison’s disease?
- Lethargy, weakness, anorexia, N&V, weight loss
- Salt craving
- Hyponatraemia and hyperkalaemia
- Hyperpigmentation, esp palmar creases
- Vitiligo
- Loss of pubic hair in women
- Hypotension, hypoglycaemia
What are the causes of hypoadrenalism?
- Primary = AI, TB, Malignancy, Waterhouse Friedrichsen, HIV, Antiphospholipid syndrome
- Secondary = pituitary
- Tertiary = hypothalamic
- Exogenous glucocorticoid therapy
What are some causes of thyrotoxicosis?
- Graves
- TMN
- Amiodarone
- Acute phase of subacute thyroiditis
- Acute phase of post-partum thyroiditis
- Acute phase of Hashimoto’s thyroiditis
What are examples of GLP-1 agonists?
Exenatide and Liraglutide
What is the MOA of GLP-1 agonists?
Increase insulin secretion and inhibits glucagon secretion
What is GLP1 physiologically?
A hormone released by he small intestine in response to an oral glucose load
How is exenatide given?
SC injection within 60 mins before the morning and evening meals
What are some examples of DPP4 inhibitors?
Sitagliptin, vildagliptin
What is the inheritance of CAH?
Autosomal recessive
What are the causes of CAH?
- 21-hydroxylase deficiency (90%)
- 11b-hydroxylase deficiency (5%)
- 17-hydroxylase deficiency (very rare)
What is CAH?
A group of autosomal recessive disorders affecting adrenal steroid biosynthesis
What biochemical abnormalities are seen in CAH?
Hyponatraemia, hyperkalaemia
How much is life expectancy reduced with T1DM?
13 years
What is the HbA1c target in T1DM?
48mmol/mol (6.5%)
How often should blood glucose be self monitored in T1DM?
At least 4 times a day (before each meal and before bed)
What are the blood glucose targets in T1DM?
- 5-7mmol/l on waking
2. 4-7mmol/l before meals at other times of the day
When should metformin be added in T1DM?
If BMI >= 25 kg/m2
What is the most common presentation of MEN1?
Hypercalcaemia
What mutation causes MEN2?
RET oncogene
What is the effect of insulin?
Causes cells in the liver, skeletal muscles and fat tissue to absorb glucose from the blood
- In liver and skeletal muscles, glucose is stored as glycogen
- In adipocytes it is stored as triglycerides
What is the structure of insulin?
A dimer of an A-chain and a B-chain, which are linked together by disulfide bonds
How is insulin synthesises?
Pro-insulin is formed by the rough endoplasmic reticulum in pancreatic beta cells –> pro-insulin is cleaved to form insulin and C-peptide –> insulin is stored in secretory granules and released in response to Ca2+
What are some effects of insulin?
- Glucose utilisation and glycogen synthesis
- Inhibits lipolysis
- Reduces muscle protein loss
- Increases cellular uptake of K via stimulation of Na/L ATPase pump
What inhibits release of prolactin?
Dopamine
What drug may be used to control galactorrhoea?
Bromocriptine (DA agonist)
What are some features of excess prolactin?
- Men = impotence, loss of libido, galactorrhoea
2. Women = amenorrhoea, galactorrhoea
What are causes of a raised prolactin?
6 Ps, OA
- Prolactinoma
- Pregnancy
- Physiological = stress/exercise/sleep
- PCOS
- Primary hypothyroidism (due to TRH stimulating prolactin release)
- Phenothiazines, metocloPramide, domPeridone
- Oestrogens
- Acromegaly (1/3rd)
What are some drugs that cause a raised prolactin?
- Metoclopramide, domperidone
- Phenothiazines
- Haloperidol
- Very rare = SSRIs, opioids
What are the BP targets for T2DM?
- No organ damage = <140/80
2. End-organ damage = <130/80
What is the MOA of SGLT2 inhibitors?
Increase urinary excretion of glucose by reducing glucose absorption in the PCT (additional 70g of glucose excreted per day), alongside some diuresis which may lower BP
What is an example of an SGLT2 inhibitor?
Empagliflozin
What are some s/es of empagliflozin?
- Urinary and genital infection
- Normoglycaemic ketoacidosis
- Increased risk of lower limb amputation
What are 3 hormones that are reduced as part of a stress response?
- Insulin
- Testosterone
- Oestrogen
What is the 1st line treatment for pts with a pituitary tumour causing acromegaly?
Trans-sphenoidal surgery
What can be used for treatment of acromegaly if surgery fails/tumour is unresectable?
Somatostatin analogues and Dopamine agonists
What is an example of a somatostatin analogue?
Octreotide
What is an example of a dopamine agonist?
Bromocriptin
What is a new medical therapy for management of acromegaly?
Pegvisomant, a GH receptor antagonist
What diabetic medication is associated with an increased risk of osteoporosis?
Thiazolidinediones
Biguanide example?
MEtformin
S/e of metformin?
- GI upset
2. Lactic acidosis in those w/ renal failure
Sulfonylurea s/e?
Gliclazide
S/es of sulfonylureas?
- Weight gain
2. Hypoglycaemia
What is the normal value for TSH?
0.5-5.5 mu/l
What is the normal value for free T4?
9-18 pmol/l
What is the management of Graves disease?
- Ant-thyroid drugs e.g. Carbimazole
- Block and replace regimes
- Radioiodine
- Surgery
- Propranolol
What is the ATD titration for Graves?
- Carbimazole started at 40mg and reduced gradually to maintain euthyroidism
- Typically continued for 12-18ms
- Fewer s/e than B&R regimes
What is the block and replace regime for Graves?
- Carbimazole started at 40mg
- Thyroxine added when pt is euthyroid
- Tx typically lasts for 6-9 months
What are some c/i’s to radioiodine tx?
- Pregnancy
2. <16 y/o
What medication is useful for T2DM pts who are obese?
DPP4 inhibitors
What is an important differential for being ‘drunk’?
Hypoglycaemia
What is the definition of hypoglycaemia?
Plasma glucose level of 3mmol/L or less
What are the most common causes of hypoglycaemia in a diabetic pt?
Insulin/sulfonylurea tx with an increase in activity or missed meal or non-accidental OD
What are some causes of hypoglycaemia in a non-diabetic pt?
ExPLAIN 1. Exogenous drugs 2 Pituitary insufficiency 3. Liver failure 4. Addison's 5. Islet cell tumours 6. Non-pancreatic neoplasms
What are some exogenous drugs that can cause hypoglycaemia in a non-diabetic pt?
- Alcohol
- Aspirin
- Pentamidine
- Quinine sulfate
- ACEi
What is DM?
A chronic condition characterised by abnormally raised levels of glucose
What are the microvascular complications of DM?
- Retinopathy
- Nephropathy
- Neuropathy
What are the macrovascular complications of DM?
- IHD
- Stroke
- PVD
What is LADA?
- Latent autoimmune diabetes of adults
2. T1DM diagnosed in later life
What are some medical causes of diabetes?
- Chronic pancreatitis
2. Haemochromatosis
What is the MOA of insulin?
- Increases insulin sensitivity
2. Decreases hepatic gluconeogenesis
In what pts can metformin not be used?
eGFR < 30ml/min
What is the MOA of sulfonylureas?
Stimulate pancreatic beta cells to release insulin
What are 3 s/es of sulfonylureas?
- Hypoglycaemia
- Hyponatraemia
- Weight gain
Sulfonylurea example?
Gliclazide
Thiazolidinedione example?
Pioglitazone
What are 4 s/es of thiazolidinediones?
- Weight gain
- Fluid retention
- Liver impairment (monitor LFTs)
- Bladder cancer
What is the MOA of DPP4 inhibitors?
Increases incretin levels which inhibit glucagon secretion
What is the 1st line test for acromegaly?
Serum IGF-1 levels
What used to be the 1st line test for acromegaly?
OGTT with serial GH measurements (now used to confirm the diagnosis if IGF1 levels are raised)
OGTT results in normal person and acromegaly?
- Normal = GH suppressed to <2 mu/L
2. Acromegaly = no suppression of GH
What causes acromegaly?
- Pituitary adenoma (95%)
- Ectopic GHRH
- GH by tumour e.g. pancreatic
What are some features of acromegaly?
- Face = coarse facial appearance, large tongue, prognathism, interdental spaces
- Hands = spade like hands
- Feet = increase in shoe size
- Skin = excessive sweating and oily skin (sweat gland hypertrophy)
- Tumour effects = hypopituitarism, headaches, bitemporal hemianopia, galactorrhoea
What proportion of acromegalic pts have a raised prolactin?
1/3rd
What percentage of pts with acromegaly have MEN1?
6%
What are 4 complications of acromegaly?
- HTN
- Diabetes
- Cardiomyopathy
- Colorectal cancer
What is Cushing’s syndrome?
A collection of signs and symptoms due to prolonged exposure to cortisol
What is Cushing’s disease?
A specific type of Cushings syndrome characterised by increased ACTH production because of a pituitary adenoma
How can you classify the causes of Cushing’s syndrome?
- ACTH dependent
- ACTH independent
- Pseudo-Cushing’s
ACTH dependent causes of Cushing’s?
- Cushing’s disease (80%)
2. Ectopic ACTH (10%) e.g. small cell lung cancer
ACTH independent causes of Cushing’s?
- Iatrogenic = steroids
- Adrenal adenoma
- Adrenal carcinoma
- Carney complex
- Micronodular adrenal dysplasia
What is Pseudo-Cushing’s?
Condition that mimics Cushing’s, often due to alcohol excess or severe depression
- Causes false positive dexamethasone suppression test or 24hr urinary free cortisol
- Insulin stress test may be used to differentiate
What are 3 conditions associated with secondary hypothyroidism?
- Downs
- Turners
- Coeliac disease
Clubbing with hyperthyroidism?
Graves
What diabetic medication is associated with an increased risk of bladder cancer?
Thiazolidinediones
What should be done to long-term steroid dosage during intercurrent illness?
Doubled
In what pts should steroid withdrawal be done gradually?
- Pts receiving >40mg prednisolone daily for >1wk
- Received more than 3 weeks treatment
- Recently received repeat courses
First line insulin regime in newly diagnosed adults with T1DM?
Basal bolus insulin regimen with twice daily insulin detemir
What is the effect of iron on TFTs?
Iron reduces the absorption of thyroxine –> raised TSH, low T4
What are 4 s/es of thyroxine therapy?
- Hyperthyroidism
- Reduced bone mineral density
- Worsening of angina
- AF
What are some interactions of thyroxine therapy?
Iron and calcium carbonate –> absorption of levothyroxine reduced –> give at least 4 hours apart
Levothyroxine starting dose?
50-100mcg OD
Levothyroxine starting dose in >50y/o OR IHD?
25mcg OD and dose slowly titrated
TSH aim during thyroxine therapy?
0.5-2.5 mU/l
Thyroxine dose during pregnancy?
Increase by at least 25-50mcg
What medication OD causes hyperinsulinaemia and high C peptide levels?
Gliclazide (it functions by releasing vesicles stored within the pancreas containing insulin and C-peptide)
What is the management of bilateral adrenocortical hyperplasia?
Spironolactone
Inheritance of MODY?
AD
MOA of orlistat?
Pancreatic and gastric lipase inhibitor to reduce digestion of fat
What is the management of obesity?
- Conservative = diet and exercise
- Medical = orlistat
- Surgical
What is the criteria for orlistat prescription?
- BMI > 28 w/ RFs
2. BMI > 30
How long is orlistat usually used for?
<1 year
Mx of a child with palpable abdo mass or unexplained enlarged abdo organ?
Refer very urgently (<48hr) for specialist assessment for neuroblastoma and Wilms’ tumour
Most common location for neuroblastoma to arise?
Neural crest tissue of adrenal medulla
Diagnosis of neuroblastoma?
- Raised vanillylmandelic acid (VMA) and homovanillic acid (HVA) levels
- Calcification on AXR
- Biopsy
Why was the rosiglitazone withdrawn in 2010?
Concerns about CVS s/e profile
How can the severity of Graves eye disease be rated?
NOSPECS
- No signs/symptoms
- Only signs e.g. upper lid retraction
- Signs and symptoms
- Proptosis
- Extra-ocular muscle involvement
- Corneal involvement
- Sight loss due to optic nerve involvement
Trousseau’s sign?
Carpal spasm on inflation of BP cuff to pressure above systolic, due to hypocalcaemia
Chvostek’s sign?
Tapping over parotid (CN7) causes facial nerves to twitch due to hypocalcaemia
Froment’s sign is a sign of?
Ulcer nerve palsy
Finkelstein’s sign is a sign of?
De Quervain’s tenosynovitis
Primary hypoparathyroidism management?
Alfacalcidol
Symptoms of hypoPT?
- Tetany = muscle twitching, cramping, spsm
- Perioral paraesthesia
- Trousseau’s sign
- Chvostek’s sign
- ECG = prolonged QT
- Chronic = depression, cataracts
What causes pseudohypoparathyroidism?
Target cells being insensitive to PTH due to abnormality in a G protein
3 associations of pseudohypoparathyroidism?
- Low IQ
- Short stature
- Shortened 4th and 5th metacarpals?
Pseudohypoparathyroidism on bloods?
Low calcium, high phosphate, high PTH
Dx of Pseudohypoparathyroidism?
- Measuring urinary cAMP and phosphate levels following an infusion of PTH
- HPT = increase in cAMP and PO4
- PseudoHPT = both low/only PO4 low
Dx of pseudopseudohypoparathyroidism?
Similar to pseudohypoparathyroidism but normal biochemistry
Addisons pt unwell?
Double the glucocorticoids
Mx of Addisons?
- Hydro and fludrocortisone
- MedicAlert bracelet
- Double dose of hydro during illness
Why can steroids worsen diabetic control?
Due to their anti-insulin effects
What is gynaecomastia?
An abnormal amount of breast tissue in males and is usually caused by an increased oestrogen:androgen ratio
Causes of gynaecomastia?
- Physiological (puberty)
- Drugs
- Syndromes = Kallman’s, Klinefelters
- Liver disease
- Testicular disease = mumps, seminoma secreting hCG
- Hyperthyroidism
- Haemodialysis
What drugs can cause gynaecomastia?
- Spironolactone
- Digoxin
- Cannabis
- Finasteride
- GnRHa e.g. goserelin
- Oestrogens
- Anabolic steroids
- Cimetidine
What is the most common drug cause of gynaecomastia?
Spironolactone
What percentage of Graves pts have eye disease?
30%
Signs of Cushings with normal dexamethasone suppression test?
Chronic alcohol abuse (Pseudo-Cushings)
ABG of Conn’s syndrome?
Metabolic alkalosis with hypokalaemia
ABG of Cushing’s?
Hypokalaemic metabolic alkalosis
Cushing’s syndrome dx?
- Overnight dexamethasone suppression test (most sensitive)
2. 24hr urinary free cortisol
Cushing’s syndrome localisation test?
- 9am and midnight plasma ACTH OR
2. Low and high dose dexamethasone suppression test
Cushings, suppressed 9am and midnight plasma ACTH?
Suppressed ACTH = adrenal adenoma (non-ACTH dependent cause)
Interpretation of low and high dose dexamethasone suppression tests for Cushings?
- Not suppressed by low dose = Cushing’s syndrome not due to primary causes, i.e. likely secondary to corticosteroid therapy
- Suppressed only by high dose = Cushings disease
- Not suppressed = Ectopic ACTH
Hormonal management of Turners?
GH
3 s/es of GH therapy?
- Headache
- Benign intracranial HTN
- Fluid retention
GH indications?
- Proven GH deficiency
- Turners
- Prader-Willi
- Chronic renal insufficiency before puberty
Erratic blood glucose control, bloating, and vomiting?
Gastroparesis
How does gastroparesis occur?
Diabetic neuropathy of the vagus nerve causing abnormal gut movement
How can you distinguish b/w MODY and T1DM?
Measure C-peptide
What syndrome is acromegaly associated with?
MEN1
Severe hyperglycaemia, dehydration and AKI, mild/absent ketonuria?
HHS
What are the DM sick day rules?
- Blood glucose monitoring 4hrly
- 3L fluid intake/24hrs
- Struggling to eat –> sugary drinks to maintain carb intake
- Box of ‘sick day supplies’
- Access to a mobile phone has been shown to reduce progression of ketosis to diabetic ketoacidosis
2 causes of central scotoma?
- Macular degeneration
2. Optic neuritis
Addisonian crisis hyper or hypotension?
Hypertension
Does a negative pituitary MRI rule out Cushing’s disease?
No - adenoma often too small to be picked up on imaging
1st line mx of symptomatic cerebral metastases?
High dose dexamethasone to reduce cerebral oedema
How can you differentiate b/w DKA and HHS by looking at bloods?
HHS does NOT cause metabolic acidosis or hyperketonaemia
Thiazide effect on calcium?
Hypercalcaemia
When must levothyroxine be taken re food?
30 mins before food as absorption may be affected by food, caffeine, or other meds
What must be done if an incidentaloma is found, even if asymptomatic?
Lab investigation must be undertaken to determine if it is functional or non-functional
Postmenopausal woman with a fracture mx?
Bisphosphonates
Best test to diagnose Addisons?
Short Synacthen test
E- abnormalities in Addisons?
- Hyperkalaemia
- Hyponatraemia
- Hypoglycaemia
- Metabolic acidosis
What is a short synacthen test?
Plasma cortisol measured before and 30 mins after giving Synacthen 250ug IM
What adrenal autoantibody may be found in Addisons?
anti-21-hydroxylase
Hypoglycaemia w/ impaired GCS mx?
100ml 20% glucose IV stat
2 main physiological responses to hypoglycaemia?
- Hormonal = decreased insulin, increased glucagon secretion, LATER GH and cortisol release
- Sympathoadrenal = = increased catecholamine and acetylcholine neurotransmission in CNS and PNS
What is the treatment of choice for toxic multinodular goitre?
Radioiodine
Why can splenectomy give a falsely high HbA1c?
Due to the increased lifespan of RBCs
What 2 main factors determine HbA1c?
- Average blood glucose conc.
2. RBC lifespan
3 conditions that cause lower than expected HbA1c?
- Sickle cell
- G6PDD
- Hereditary spherocytosis
3 causes of higher than expected HbA1c levels?
- Vit B12/folic acid deficiency
- IDA
- Splenectomy
Hypothermia, hyporeflexia, bradycardia, seizures?
Myxoedema coma
What is the first line treatment for prolactinomas?
DA agonists e.g. carbergoline, bromocriptine
What should every person treated with insulin also be given for emergencies?
A glucagon kit
Mx of conscious hypoglycaemia?
10-20g of short acting carbohydrate e.g. one glass of glucozade or non-diet drink, 3 or more glucose tablets, glucose gel
What is Zollinger-Ellison syndrome?
Rare condition caused by gastrin-secreting tumour found in either the islet cells of the pancreas or in the duodenal wall
Management of diabetic gastroparesis?
Metoclopramide, domperidone, erythromycin (all prokinetic agents)
What is the maximum dose of metformin?
1g BD
Most common cause of impaired hypoglycaemia awareness in a pt with long-standing type 1 diabetes?
Neuropathy of the autonomic nervous system
Acute management of DKA?
Fixed rate insulin 0.1mg/kg/hr, continue long acting insulin but stop short acting insulin
Mx of thyrotoxic storm?
- IV propranolol (for tachy)
- Propylthiouracil (anti-thyroid)
- IV Dexamethasone (blocks T4 to T3 conversion, also treats any underlying adrenal insufficiency)
- Underlying cause
Precipitating events of a thyroid storm?
- Thyroidal/non-thyroidal surgery
- Trauma
- Infection
- Acute iodine load e.g. CT contrast media
Clinical features of thyroid storm?
- Fever > 38.5
- Tachy
- Confusion and agitation
- N&V
- HTN
- HF
- Abnormal LFTs/jaundice
Most common metabolic complication of cancer?
Hypercalcaemia
Why is dexamethasone used for brain tumours?
Anti-inflammatory effects of corticosteroids but minimal mineralocorticoid (fluid retention) effects
What is the 4th most abundant cation in the body?
Magnesium
How much Mg is in the body?
1000mmol
Pt with malabsorption and low calcium, why?
Malabsorption –> magnesium deficiency –> low calcium
Why does low Mg cause low Ca?
- Mg is required for both PTH secretion and its action on target tissues
- Mg and Ca interact at a cellular level also and as a result decreased magnesium will tend to affect the permeability of cellular membranes to calcium, resulting in hyperexcitability
Hypokalaemia, hypernatraemia, and HTN?
Primary hyperaldosteronism
What are the gliptins?
Dipeptidyl peptidase 4 (DPP4) inhibitors