Endocrinology Flashcards

Question

How often should someone with type 2 diabetes mellitus have their HbA1c checked and what targets should they aim for?

Answer 1

Monitor HBA1C every 3-6 months until stable and then every 6 months. If managing with just lifestyle or lifestyle and metformin then HbA1c target is 48mmol/l or 6.5%, if managing with any drugs that can cause hypoglycaemia then the target is 53mmol/l or 7%. IN the elderly consider relaxing these targets.

Answer 2

Treatment of T2DM • Lifestyle modification (diet, weight control and exercise) • Metformin and titrate up or down as required • If hbA1c rises above 58mmol/mol, dual therapy with metformin and: 1. DPP4 inhibitor (gliptin) 2. Thiazolidinedione (glitazone) 3. Sulphonylurea 4. SGLT-2i (gliflozin) • If hbA1c rises again to above 58mmol/mol, triple therapy with metformin and: 1. DPP4 inhibitor (gliptin) and a sulphonylurea 2. Thiazolidinedione (glitazone) and a sulphonylurea 3. Sulphonylurea and SGLT-2i (gliflozin) 4. Thiazolidinedione and a SGLT-2i (gliflozin) 5. Insulin therapy • If triple therapy not effective, not tolerated or contraindicated and BMI > 35 then metformin, +sulphonylurea + GLP-1 mimic

Answer 3

When metformin not tolerated or contraindicated • If the HbA1c rises to 48 mmol/mol (6.5%) on lifestyle interventions, consider one of the following: 1. sulfonylurea 2. gliptin 3. pioglitazone • If the HbA1c has risen to 58 mmol/mol (7.5%) then one of the following combinations should be used: 1. gliptin + pioglitazone 2. gliptin + sulfonylurea 3. pioglitazone + sulfonylurea • If despite this the HbA1c rises to, or remains above 58 mmol/mol (7.5%) then consider insulin therapy

Answer 4

Blood pressure is now controlled at the same levels as other patients - < 140/90. Note, unless afro-Caribbean ACEi are always first line in diabetics due to the renoprotective effect.

Answer 5

Insulin therapy When starting insulin in T2DM metformin should be continued whilst other drugs should be reviewed. Recommendations are to start with human NPH insulin taken at bedtime or twice daily when needed.

Answer 6

Is usually stopped on admission to hospital and be wary of lactic acidosis and GI symptoms (consider modified release). Taken orally as a tablet that increases insulin sensitivity and decreases hepatic gluconeogenesis. Cannot causes hypoglycaemia.

Answer 7

Stimulate pancreatic beta cells to secrete insulin, given as an oral tablet. SE include hypoglycaemia, increased appetite, and weight gain SIADH, and liver dysfunction (cholestatic). Examples include gliclazide and glimepiride.

Answer 8

Activate PPAR-gamma receptor in adipocytes to promote adipogenesis and fatty acid uptake. Taken orally as a tablet. SE include weight gain, fluid retention, liver dysfunction, bladder cancer risk and fractures. Only currently available drug is pioglitazone.

Answer 9

Increases incretin levels which inhibit glucagon secretion. Taken orally as a tablet. SE are rare but there is an increased risk of pancreatitis. Does not cause weight gain. Examples include Vildagliptin and sitagliptin.

Answer 10

SGLT-2 inhibitors - inhibit reabsorption of glucose in the kidneys, take orally as a tablet. SE include UTI, normoglycemic ketosis and increased risk of amputation – monitor feet closely. Preferred by patients as they often result in weight loss. Examples include canagliflozin, dapagliflozin and empagliflozin.

Answer 11

Incretin mimic which inhibits glucagon secretion, given SC. SE include nausea, vomiting and pancreatitis. Also liked by patients as they result in weight loss. Examples include Exenatide. Given within 60 minutes before the morning and evening meals, do not given after a meal.

Answer 12

* Increase frequency of CBG to four hourly or more often * Drink plenty of fluid * If unable to eat maintain carbohydrates with sugary drinks * Always have access to a mobile phone * Do not stop oral hypoglycaemics even if intake is low (stress response increases glucose levels). Only exception is metformin if dehydrated due to renal impact. * If on insulin never stop due to risks of DKA

Answer 13

Manufacturing process Porcine – extracted and purified from pig pancreas Human sequence insulin – either produced by enzyme modification of porcine insulin (emp) or biosynthetically by recombinant DNA using bacteria (crb, prb) or yeast (pyr) Analogues Duration of action Rapid-acting insulin – onset in 5 mins, peak in 1 hour and duration of 3-5 hours Short-acting insulin – onset in 30mis, peak at 3 hours and duration 6-8 hours Intermediate-acting insulin – onset in 2 hours, peak at 5-8 hours and duration 12-18 hours Long-acting insulin analogues – onset in 1-2 hours, flat profile and duration up to 24 hours

Answer 14

Novomix 30 – 30% aspart (rapid) and 70 aspart protamine (intermediate) Humalog Mix25 – 25% lispro (rapid) and 75% lispro protamine (intermiedate) Humulin M3 – 30% soluble isophane (short) and 70% isophane (intermediate)

Answer 15

Vast majority of insulin is given SC and it is important to rotate injection sites to prevent lipodystrophy. Insulin pumps are available which delivers continuous basal infusion and patient activated bolus doses at meal times.

Answer 16

Lifestyle modifications At least yearly follow-up with blood tests Metformin if adult at high risk if despite lifestyle modifications their results are not improving or getting worse.

Answer 17

To hold a HGV license the following standard must be met 1. No severe hypoglycaemic events in the last 12 months 2. Driver is fully hypoglycaemic aware 3. Adequate control of condition by regular monitoring at least twice daily and times relevant to driving – done using a device with a memory function 4. Shows understanding of the risks of hypoglycaemia For driving regular vehicles whilst taking insulin 1. Hypoglycaemic aware 2. No more than one episode of hypoglycaemia requiring assistance in the past 12 months 3. No relevant visual impairment If on any tablets that can induce hypoglycaemia then there must have been no more than one episode of hypoglycaemia requiring assistance in the past 12 months. For any other tablets there is no need to make the DVLA aware

Answer 18

This occurs due to peripheral neuropathy and peripheral arterial disease which can both occur in diabetes.

Answer 19

Loss of sensation Absent pulses Reduced ABPI Intermittent claudication

Answer 20

All patients with diabetes should be screened annually by checking for ischaemia – palpating both pulses in the foot and screening for loss of sensation.

Answer 21

Low risk – no risk factors except callus alone Moderate risk – deformity or neuropathy or non-critical limb ischaemia High risk – previous ulceration or amputation, on dialysis, neuropathy, and non-critical limb ischaemia together or either combined with a callus/deformity Anyone who is moderate or high risk should be followed up by local diabetic foot centre

Answer 22

Starvation state in which the body converts fats into ketones for use by the brain. Primarily this occurs in type 1 DM and is often how it first presents. Occasionally it can occur in type 2 under conditions of extreme stress.

Answer 23

Lack of available glucose to cells due to insulin deficiency or resistance. Risk of euglycemic DKA with SGLT-2 inhibitors (gliflozins). This can be triggered by: infection, surgery, MI, pancreatitis, chemotherapy, antipsychotics, wrong insulin dose, missed doses and non-compliance.

Answer 24

``` Gradual drowsiness Vomiting Dehydration Abdominal pain Polyuria and polydipsia Ketoic breath Kussmaul respiration (deep hyperventilation) Coma and deep sleeps Acidaemia Hyperglycaemia Ketonaemia and/or Ketonuria ```

Answer 25

``` ABG Blood glucose Serum ketones or urine dipstick ECG and chest x-ray Serum and urine osmolality if indicated ```

Answer 26

Glucose > 11.1mmol/l or known DM pH < 7.3 Bicarbonate < 15mmol/l Ketones > 3 mmol/l or urine ketones ++ on dipstick

Answer 27

If severe DKA then immediate review by a senior and consider HDU/ITU admission. Severe DKA indicated by blood ketones > 6mmol/L, Venous bicarbonate <5mmol/L, pH < 7, Potassium < 3.5mmol/L on admission, GCS < 12/abnormal AVPU/EWS > 6, O2 sats on air < 92%, Systolic BP < 90, Pulse > 100 or < 60, or anion gap above 16.

Answer 28

1. Fluid replacement with isotonic saline initially (be wary of cerebral oedema in the young), give first litre over 1 hour then follow the proforma 2. IV Insulin 50U in 50ml saline at 0.1U/kg/h fixed rate. If likely to be delay >15mins in administration of fixed rate insulin then give STAT 10 units SC or IM. 3. Switch to variable rate insulin once ketones are < 0.6mmol/l 4. Once blood glucose is <14mmol/l start 10% dextrose at 125ml/hour and review rate of saline to avoid overload 5. Continue patients regular long-acting insulin but stop their short acting 6. Correct hypokalaemia and monitor potassium levels closely – < 5.5 give replacement in the saline, <3.5 senior review and if >5.5 no potassium should be given. 7. Prescribe thromboprophylaxis

Answer 29

``` Complications Gastric stasis Thromboembolism Arrhythmias secondary to potassium derangement ARDS AKI ```

Answer 30

This is a medical emergency and usually tricky to manage with a significant mortality. Out of control hyperglycaemia results in an osmotic diuresis leading to severe dehydration and electrolyte deficiencies. Typically, this presents in the elderly with and usually with T2DM but is increasingly common in the young and like DKA can be the original presentation of T2DM.

Answer 31

* Hyperglycaemia results in osmotic diuresis with associated loss of sodium and potassium * Severe volume depletion results in a significant raised serum osmolarity (typically > than 320 mosmol/kg), resulting in hyperviscosity of blood. * Despite these severe electrolyte losses and total body volume depletion, the typical patient with HHS, may not look as dehydrated as they are, because hypertonicity leads to preservation of intravascular volume.

Answer 32

This presents over a number of days and so the dehydration and metabolic disturbance are often worse than in DKA. Fatigue and lethargy Nausea and vomiting Diagnosis Blood glucose levels > 30mmol/l without significant ketonaemia (<3mmol/l or urine ketones < 2+) or acidosis (pH >7.3) Raised osmolality >320mosmol/kg (2Na + glucose + urea) Hypovolaemia

Answer 33

``` Extremely important to differentiate between HHS and DKA ABG Blood glucose Blood ketones Urine dipstick Serum osmolality ```

Answer 34

To manage HHS we must normalise osmolality gradually, replace fluid and electrolytes and normalise blood glucose gradually. Fluid loss is usually 100-220ml/kg. 1. IV fluids – normal saline of 1l in the first hour then follow the proforma. Only switch to 0.45% under direction of a senior if 0.9% has not had the desired response i.e. osmolality increasing (or decreasing by <3mosmol/kg/h) and Na is increasing. Aim for a positive fluid balance of 2-3l by 6 hours, 3-6l by 12 hours and replacement of the rest over the remaining 12 hours. 2. Catheterise within first hour to monitor output 3. Fixed rate insulin 50U in 50ml saline given at 0.05U/kg/h ONLY if significant ketonaemia is present (>1mmol/l) or ketonuria > ++ or glucose levels dropping by <5mmol/l/h despite adequate fluid replacement. Withhold all normal anti-diabetic and insulin regimes if starting IV insulin 4. Correct hypokalaemia and monitor potassium levels closely – < 5.5 give replacement in the saline (20mmol in 500ml), <3.5 senior review and if >5.5 no potassium should be given. 5. Once blood glucose is <14mmol/l start 10% dextrose at 62.5ml/hour and review rate of saline to avoid overload 6. Glucose levels should not fall faster than 4-6mmol/h and sodium rising is only a concern if osmolality is not declining at the same time 7. Aim for target blood glucose of 10-15mmol/l 8. Complete normalisation of electrolytes and osmolality may take 72 hours

Answer 35

MI, stroke, and peripheral arterial thrombosis Seizures Cerebral oedema Central pontine myelinolysis if serum osmolality declines too quickly

Answer 36

Usually as a result of insulin overdose. Some tablet medications can cause hypos such as sulphonylureas.

Answer 37

``` Sweating and trembling Hungry Anxiety Poor concentration Palpitations Tingling of lips and pale Vague/confused Convulsions Coma ```

Answer 38

Mild – adults who are conscious, orientated, and able to swallow 1. Glucojuice 2. Cold high sugar drink – 150-200ml 3. Dextrose tablets 4. Test CBG 10-15mins later, if still <4mmol/l then repeat up to maximum of 3 times 5. If till hypoglycaemic, consider glucagon 1mg IM or 150-200ml of 10% IV glucose over 15 minutes 6. Once CBG > 4mmol/l give long-acting carbohydrate but do not omit insulin dose, if due give after meal 7. Recheck CBG in 30-60mins and regularly for the next 48hours

Answer 39

Moderate – patients conscious and able to swallow but confused, agitated or aggressive 1. If capable treat as mild 2. If not capable and cooperative give 1.5-2tubes of glucose gel 3. Test CBG 10-15mins later, if still <4mmol/l then repeat up to maximum of 3 times 4. If still hypoglycaemic, consider glucagon 1mg IM or 150-200ml of 10% IV glucose over 15 minutes 5. Once CBG > 4mmol/l give long-acting carbohydrate but do not omit insulin dose, if due give after meal 6. Recheck CBG in 30-60mins and regularly for the next 48hours

Answer 40

Severe – patient unconscious/aggressive/NBM or CBG < 2.6mmol/l 1. Check ABCDE 2. Stop IV insulin 3. Secure IV access and give 75ml or or 150-200ml of 10% IV glucose over 15 minutes 4. Consider IM glucagon in the absence of IV access 5. Re-check CBG after 10mins and if remains <4mmol/l repeat IV glucose or consider glucose infusion 50ml/hr 6. Recheck CB and medical review 7. Restart IV insulin infusion once CBG >4mmol/l

Answer 41

Cushing’s syndrome occurs due to excess cortisol resulting in a classical set of symptoms due to imbalance in the adrenocortical hormones.

Answer 42

ACTH dependant causes 1. Cushing’s disease (80%) pituitary tumour secreting ACTH producing adrenal hyperplasia 2. Ectopic ACTH production (5-10%) such as small cell lung cancer – characteristically has very low hypokalaemia

Answer 43

ACTH independent causes 1. Iatrogenic from chronic steroid use – by far the most common cause of Cushing’s syndrome 2. Adrenal adenoma (5-10% 3. Adrenal carcinoma (rare) 4. Carney complex – syndrome including cardiac myxoma 5. Micronodular adrenal dysplasia (very rare)

Answer 44

Mimics of Cushing’s syndrome, often due to alcohol excess or severe depression. Causes false positive dexamethasone suppression test or 24hr urinary free cortisol. Insulin stress test can be used to differentiate.

Answer 45

Cushingoid appearance: Moon face, central obesity and wasted limbs (lemon on two sticks), buffalo hump, supraclavicular fat pads, skin and muscle atrophy, bruises and purple abdominal striae Mood changes including depression, lethargy, irritability, and psychosis Osteoporosis Proximal weakness Recurrent Achilles tendon rupture Gonadal dysfunction Hypertension Hypokalaemic metabolic alkalosis with a raised bicarbonate Hypernatremia Impaired glucose tolerance due to insulin resistance

Answer 46

Confirmation tests • Overnight dexamethasone suppression test • 24hr urinary free cortisol • Insulin stress test

Answer 47

Localisation tests • 9am and midnight plasma ACTH (and cortisol) levels – if ACTH is suppressed then a non-ACTH dependant causes is likely • Low or high dose 48hour dexamethasone suppression test • CRH stimulation – if pituitary source then cortisol rises, if ectopic/adrenal then no change in cortisol

Answer 48

Normal (inhibition) in low dose dexamethasone Normal (inhibition) in high dose dexamethasone test Normal ACTH levels

Answer 49

Normal (no inhibition) in low dose dexamethasone Low (inhibition) in high dose dexamethasone test Raised ACTH levels

Answer 50

Low (no inhibition) in low dose dexamethasone Low (no inhibition) in high dose dexamethasone test Raised ACTH levels

Answer 51

Low (no inhibition) low dose dexamethasone Low (no inhibition) high dose dexamethasone test Low ACTH levels

Answer 52

Potassium regulated by 3 main factors- aldosterone, insulin, and acid base balance. Dietary causes of hyperkalaemia are rare, foods that are high in potassium include salt substitutes which contain potassium instead of sodium, bananas, oranges, kiwi, avocado, spinach and tomatoes.

Answer 53

``` AKI Drugs – ACE inhibitors, ARB, spironolactone and amiloride, ciclosporin, heparin (both types due to inhibition of aldosterone) and beta blockers in renal failure Rhabdomyolysis Metabolic acidosis Iatrogenic Addison’s disease Large blood transfusion Burns ```

Answer 54

``` ECG Changes • Tall, tented T waves • Wide QRS complex that can become sinusoidal and asystole • Small or absent P waves • Sine wave appearance ``` ``` Fast irregular pulse Chest pain Weakness Palpitations Light headedness ```

Answer 55

ECG ABG/VBG Us and Es

Answer 56

``` 12 lead ECG monitoring Stop potassium sparing diuretics Low Potassium diet IV 10ml of 10% calcium gluconate over 5-10 minutes and repeat till ECG normalises (cardioprotective by stabilising the membrane) 50mls 50% glucose and 10 units insulin Salbutamol nebs high dose (10-20mg) ``` Calcium resonium orally or enema Loop diuretics Dialysis

Answer 57

With hypertension Cushing’s syndrome/steroids/ACTH (usually alkalotic) Conn’s Syndrome or primary hyperaldosteronism (usually alkalotic) Liddle’s syndrome 11-beta hydroxylase deficiency (21-hydroxylase deficiency which causes 90% of congenital adrenal hyperplasia does not cause hypertension)

Answer 58

Thiazide and loop diuretic (if long standing then bicarbonate will be raised - alkalotic) Vomiting (alkalotic) and Diarrhoea (acidotic) Renal Tubular acidosis type 1 and 2 Bartter’s and Gitelman syndrome Rectal villous adenoma Intestinal fistula Alkalosis

Answer 59

``` ECG Changes • Small or inverted P waves • Small or absent T waves • Depressed ST segment • Long PR interval • Prominent U waves (extra wave after p) • Long QT ``` ``` Muscle weakness and hypotonia Hyporeflexia Cramps Tetany Palpitations Light headedness ```

Answer 60

ECG ABG Us and Es

Answer 61

Magnesium is also usually low, and hypokalaemia can be hard to treat until Mg is normalised If mild: give oral K+ supplement and review after 3 days If Severe: Give IV potassium cautiously but never more than 20mmol/h *Do not give K+ if oliguric or as a fast STAT bolus dose*

Answer 62

If Phosphate high CKD Hypoparathyroidism (e.g., post thyroid/parathyroid surgery) Pseudohypoparathyroidism (target cell insensitive to PTH) Acute Rhabdomyolysis Hypomagnesia ``` If Phosphate low Vitamin D deficiency and Osteomalacia Acute Pancreatitis Over Hydration and massive blood tranfusion Respiratory Alkalosis ``` Note magnesium is required for PTH secretion and its action so hypomagnesaemia can both cause hypocalcaemia and render patients unresponsive to treatment with calcium and vitamin D

Answer 63

Tetany – muscle twitching, cramping and spasm Perioral paraesthesia Carpopedal Spasm (very panful cramps in hands and feet) Trousseau’s sign (spasm of hand when applying a BP cuff) Chvostek’s Sign – tap over parotid and facial muscles spasm Chronic depression and cataracts ECG – prolonged QT interval SPASMODIC – Spasms, Perioral paraesthesia, Anxious, Seizures, Muscle tone increased (colic, laryngospasm, and dysphagia), Orientation impaired, Dermatitis, Impetigo herpetiformis and Chvostek’s sign.

Answer 64

Treat hypomagnesaemia first if present Vitamin D Mild – give calcium 5mmol/6 hours PO Severe – give 10ml 10% calcium gluconate IV over 30 mins and repeat as necessary

Answer 65

Two causes account for 90% of cases: 1. Primary Hyperparathyroidism 2. Malignancy – bone metastases, myeloma, PTHrP from lung SCC

Answer 66

``` Sarcoidosis Acromegaly Thyrotoxicosis Drugs – lithium, thiazides and calcium containing antacids Vitamin D Toxicity Dehydration Addison’s disease Paget’s disease of the bone ```

Answer 67

Stones, Bones, Groans, Thrones and Psychiatric overtones ``` Renal Calculi Bone pain Constipation (Abdominal pain nausea and vomiting) Polyuria causing dehydration Tiredness Depression Confusion Hypertension Corneal calcification ``` High calcium and high PTH = primary or tertiary hyperparathyroidism High calcium and low PTH = malignancy or other rarer causes

Answer 68

U&Es and bone profile | ECG changes – short QT interval

Answer 69

Rehydration with normal saline, typically 3-4l a day, if can’t tolerate fluids loop diuretics are sometimes used but be aware, they don’t worsen electrolyte derangement Bisphosphonates following this Calcitonin and steroids are other options Fluids and loop diuretics which prevents calcium reabsorption however you must monitor potassium and magnesium depletion. Treat cause

Answer 70

Heart Arrhythmia Coma Hypercalcaemic crisis (anuria and coma)

Answer 71

Definition – low sodium concentrations in the blood either due to water excess or sodium depletion. Be aware of low sodium where blood has been taken from a drop arm.

Answer 72

Hypovolaemic • Diuretics • Addison’s disease • Diuretic stage of renal failure Euvolaemic • SIADH (urine osmolality >500mmol/kg) • Hypothyroidism

Answer 73

Sodium depletion due to extra renal loss • Diarrhoea, vomiting and sweating • Burns and adenoma of rectum Water excess (patent often hypervolaemic and oedematous) • Secondary hyperaldosteronism (HF and liver cirrhosis) • Nephrotic syndrome • IV dextrose • Psychogenic polydipsia

Answer 74

Mild (130-134mmol/l) – Moderate (120-129mmol/l) ``` Muscle cramps Nausea and vomiting Dizziness Malaise Headache Irritability Confusion Lethargy ```

Answer 75

Severe (<120mmol/l) Reduced GCS Seizures Coma Respiratory arrest

Answer 76

Occurs due to over-correction of severe hyponatraemia. To avoid this raise levels slowly. Symptoms usually occur after 2 days and are irreversible – dysarthria, dysphagia, paraparesis or quadriparesis, seizures, confusion, and coma. Patients are awake and aware but like locked-in syndrome.

Answer 77

Assess fluid status Routine bloods Serum and urine osmolality and U&Es

Answer 78

Mild – fluid restriction (<800ml/day) and loop diuretics Moderate – hypertonic saline in first 3-4 hours then fluid restriction and loop diuretics Severe – bolus of hypertonic saline until symptoms resolution +/- conivaptan (vasopressin/ADH receptor antagonists) note, these work on V1 and V2 receptors. Should be avoided in hypovolaemic hyponatraemia. Fluid intake should be less than urine output in HF, liver cirrhosis, SIADH, renal failure and psychogenic polydipsia

Answer 79

Dehydration Osmotic diuresis e.g., hyperosmolar non-ketotic diabetic coma Cushing’s syndrome Diabetes Insipidus Primary Aldosteronism (BP high K+ low and metabolic alkalosis) Excess IV saline

Answer 80

``` Lethargy Thirst Weakness Irritability Confusion Fits Coma ```

Answer 81

Rehydrate Reduce sodium levels slowly to avoid cerebral oedema – no greater than 0.5mmol/hr Avoid Hypertonic solutions

Answer 82

Magnesium is the 4th most common cation in the body with the majority contained within bone. Its levels are managed by PTH and aldosterone.

Answer 83

``` Drugs: diuretics, proton pump inhibitors Total parenteral nutrition Diarrhoea Alcohol Hypokalaemia and hypocalcaemia Metabolic disorders: Gitleman's and Bartter's ```

Answer 84

Often similar to hypocalcaemia as magnesium is required for both PTH secretion and its action so Hypomagnesia can both cause hypocalcaemia and render patients unresponsive to treatment with calcium and vitamin D supplementation. ``` Paraesthesia Tetany Seizures Decreased PTH secretion → hypocalcaemia ECG features similar to those of hypokalaemia ```

Answer 85

If <0.4 mmol/l then intravenous replacement. An example regime would be 40 mmol of magnesium sulphate over 24 hours. If >0.4 mmol/l then oral magnesium salts (10-20 mmol orally per day).

Answer 86

* Hashimoto’s disease – anti-thyroid peroxidase (TPO) and/or anti-thyroglobulin (Tg) antibodies – most common and associated with T1DM, Addison’s and pernicious anaemia * Iodine deficiency – uncommon in UK * Postpartum thyroiditis * Surgery to the neck * Drug induced – antithyroid drugs, amiodarone, and lithium * Riedel thyroiditis – fibrous tissue replacing normal thyroid – painless goitre * Subacute thyroiditis (de Quervain’s) – occurs following viral infection, starts hyperthyroid for 3-6weeks, then euthyroid for 1-3 weeks then hypothyroid for weeks-months and then return to normal

Answer 87

* Disorder of the pituitary | * Pituitary apoplexy

Answer 88

Goitre Cold Weight gain Sinus Bradycardia and decreased cardiac output so overall low BP Low voltage ECG Pleural/pericardial effusion Face looks round and puffy with double chin and obese Shortness of breath Constipation Mood swings – anxious and depressed Poor concentration, memory and initiative Oedema Dry skin and slow hair/nail growth (can get hair loss) Menstrual Disturbance (TSH stimulates LH and FSH and TRH stimulates prolactin by inhibiting dopamine Carpel tunnel syndrome Delayed relaxation after tendon reflexes

Answer 89

TFTs Thyroid scan High TSH low T4 Hypothyroidism High TSH normal T4 Subclinical Hypothyroidism Low TSH and low T4 Central hypothyroidism (hypothalamic or pituitary failure)

Answer 90

Levothyroxine taken 30-60mins before breakfast. Half life is 7 days so test for affect after 4 weeks of starting and then 8-12 weeks after any dose change looking for normalisation of the TSH. Levothyroxine is metabolised by CYP P450. Start at low doses in elderly and those with IHD. Main SE are hyperthyroidism, reduced bone mineral density, worsening angina and AF Subclinical hypothyroidism has no symptoms but a small risk of progressing to overt hypothyroidism. Most patients don’t require treatment but always start if <70years and TSH > 10mU/l Subacute thyroiditis does not usually require treatment

Answer 91

Myxedema Coma – rare but life threatening. Very low temperature without shivering, confusion, bradycardia, low BM and reduced breathing effort. Manage via ABCDE then levothyroxine, hydrocortisone (especially if pituitary hypothyroidism is suspected). Precipients are infection, MI stroke and trauma.

Answer 92

Subclinical hyperthyroidism – normal T3 and T4 levels but TSH below normal. Usually this Is due to a multinodular goitre in elderly females or excessive thyroxine. This is important to diagnose due to its association with atrial fibrillation and osteoporosis. Only managed if TSH persistently low and trialled with low dose antithyroid agents for 6 months.

Answer 93

* Grave’s Disease – antibody that stimulates the TSH receptor or anti-thyroid peroxidase antibodies – most common cause * Pituitary or thyroid adenoma * Toxic multinodular goiter (autonomously functioning thyroid nodules) * Acute phase of subacute (de Quervain’s) thyroiditis * Acute phase of post-partum thyroiditis * Acute phase of Hashimoto’s thyroiditis * Ectopic thyroid tissue * Amiodarone due to high iodine content causing excess iodine-induced thyroid hormone synthesis or destructive thyroiditis

Answer 94

``` Goitre Menstrual Disturbance – TSH stimulates LH and FSH and TRH stimulates prolactin by inhibiting dopamine Warm (perspiration and clammy hands) Weight loss Tachycardia Increased appetite and bowl movements Anxiety and irritable may be emotionally labile Concentration issues, panic attacks Excessive urination, drinking High blood sugar Tremors Sleeping problems Muscle weakness Thinning of the skin, fine brittle hair ```

Answer 95

Thyroid eye disease particularly exophthalmos, ophthalmoplegia and optic neuropathy Pretibial myxedmea – thickening of the skin on the shins Thyroid acropachy – clubbing and painful finger and toe swellings

Answer 96

TFTs Thyroid scan Radioiodine uptake by the thyroid Thyroid autoantibody tests Raised TSH, Raised T4 - TSH secreting tumour or thyroid hormone resistance. Low TSH, high T4 and T3 Hyperthyroidism Low TSH, normal T4 and T3 Subclinical Hyperthyroidism

Answer 97

Carbimazole/methimazole – inhibits peroxidase enzyme (SE can cause neutropenia but rare), start at high dose for 6 weeks until euthyroid then reduced Obliteration of thyroid gland using radioactive iodine Thyroidectomy Beta blockers – reduce sympathetic activation

Answer 98

Precipitated by thyroid surgery, trauma, infection or acute iodine load e.g. CT contrast

Answer 99

``` Pyrexia > 38.5C Tachycardia, hypertension, and heart failure (may develop AF) Confusion and agitation Nausea and vomiting Abnormal LFTs and sometimes jaundice Psychosis Abdominal pain ```

Answer 100

Propranolol or esmolol (ultra-short acting to prevent MI in patients with asthma/poor cardiac output)> Consider diltiazem if beta blockers contraindicated and get help Antithyroid drugs (methimazole or propylthiouracil) After 4 hours give Lugol’s Solution (aqueous iodine oral solution) Dexamethasone or hydrocortisone to prevent peripheral conversion of T4 to T3 Paracetamol to control pyrexia

Answer 101

Autosomal recessive disorder that prevents copper being excreted into bile . Defect in the ATP7B gene located on chromosome 13.

Answer 102

Usually presents in children and young adults 10-25yrs. Children usually present with liver disease whilst young adults it is neurological disease. The copper mainly accumulates into the Liver and brain leading to liver disease and psychiatric symptoms

Answer 103

Liver – causes hepatitis and chronic liver disease leading to: tiredness, hepatic encephalopathy, portal hypertension and spider naevi Brain – basal ganglia degeneration leading to problems in speech, behaviour, and psychiatric problems. Also asterixis, chorea, dementia and parkinsonian like symptoms. Eyes – Kayser-Fleischer rings – green brown copper deposit as a ring around the periphery of the iris. Also sunflower cataracts Kidneys – renal tubular acidosis, haematuria, calcium accumulation in the kidneys and subsequent osteoporosis – especially Fanconi syndrome Heart – Cardiomyopathy Other – Hypoparathyroidism, haemolysis, blue nails, infertility and habitual abortion.

Answer 104

``` LFTs Coagulation Slit lamp examination of the eyes MRI showing hyperintensities in the basal ganglia Copper and Ceruloplasmin (copper carrying enzyme) levels in blood - both of which will be low Liver biopsy is the gold standard Raised urine copper Genetic testing ```

Answer 105

Low copper diet Penicillamine – copper chelation Trientine hydrochloride is an alternative Liver transplantation

Answer 106

``` Recent thyroid surgery Radioiodine Infection MI Trauma ```

Answer 107

Carbimazole adverse effects – agranulocytosis

Answer 108

Prednisolone = predominant glucocorticoid and low mineralocorticoid activity Dexamethasone and Betamethasone = very high glucocorticoid and minimal mineralocorticoid activity

Answer 109

Glucocorticoid side-effects • Endocrine: impaired glucose regulation, increased appetite/weight gain, hirsutism, hyperlipidaemia • Cushing's syndrome: moon face, buffalo hump, striae • Musculoskeletal: osteoporosis, proximal myopathy, avascular necrosis of the femoral head • Immunosuppression: increased susceptibility to severe infection, reactivation of tuberculosis • Psychiatric: insomnia, mania, depression, psychosis • Gastrointestinal: peptic ulceration, acute pancreatitis • Ophthalmic: glaucoma, cataracts • Suppression of growth in children • Intracranial hypertension • Neutrophilia Mineralocorticoid side-effects • Fluid retention • Hypertension

Answer 110

This is a group of autosomal recessive disorders which affect adrenal steroid biosynthesis. As a result of low cortisol levels, the anterior pituitary secretes high levels of ACTH which in turn stimulates adrenal androgens which may virilize a female infant.

Answer 111

21-hydroxylase deficiency (90%) • Virilisation of female genitalia • Precocious puberty in males • 60-70% of patients have a salt-losing crisis at 1-3 weeks of age ``` 11-beta hydroxylase deficiency (5%) • Virilisation of female genitalia • Precocious puberty in males • Hypertension • Hypokalaemia ``` 17-hydroxylase deficiency (very rare) • Non-virilising in females • Inter-sex in boys • Hypertension

Answer 112

Previously thought to be most commonly caused by an adrenal adenoma, called Conn’s syndrome however it has recently emerged that bilateral idiopathic adrenal hyperplasia is the cause in 70% of cases.

Answer 113

Hypertension Hypokalaemia – muscle weakness Alkalosis

Answer 114

Plasma aldosterone/renin ratio is first line investigation (should show high aldosterone levels alongside low renin levels due to negative feedback of sodium retention) High resolution CT abdomen and adrenal vein sampling used to differentiate between unilateral and bilateral sources of aldosterone

Answer 115

Adrenal adenoma – surgery | Bilateral adrenal hyperplasia – aldosterone antagonist such as spironolactone

Answer 116

This occurs due to over activity of the renin-angiotensin system. This can be as a result of a renin releasing tumours, Juxtamedullary cell tumours, renal artery stenosis and fibromuscular dysplasia.

Answer 117

PTH elevated Ca elevated Phosphate low

Answer 118

Features - 'bones, stones, abdominal groans and psychic moans' Polydipsia, polyuria Peptic ulceration/constipation/pancreatitis Bone pain/fracture Renal stones Depression Hypertension Associated with Multiple endocrine neoplasia MEN 1 and 2 Pepper pot skill characteristic X-ray finding

Answer 119

80% of cases are due to a solitary adenoma | Multifocal disease occurs in 10-15% and parathyroid carcinoma in 1%

Answer 120

High fluid intake to prevent stones Avoid thiazides and high calcium/vitamin D diet Indications for surgery • Elevated calcium >1mg/dL above normal • Hypercalciuria >400mg/day • Creatinine clearance < 30% compared with normal • Episode of life-threatening hypercalcaemia • Nephrolithiasis • Age < 50yrs • Neuromuscular symptoms • Bone mineral density scan showing T score < -2.5

Answer 121

PTH elevated Ca low or normal Phosphate elevated Vitamin D low

Answer 122

Few symptoms | Eventually develop bone disease – osteitis fibrosa and soft tissue calcifications

Answer 123

Parathyroid gland hyperplasia occurs as a result of low calcium, almost always in setting of chronic renal failure or low vitamin D intake

Answer 124

Usually managed medically with phosphate binders and by correcting the cause Indications for surgery Bone pain Persistent pruritis Soft tissue calcifications

Answer 125

``` PTH elevated Ca normal or elevated Phosphate decreased or normal Vitamin D normal or decreased Alkaline phosphatase elevated ```

Answer 126

Metastatic calcification Bone pain and/or fracture Nephrolithiasis Pancreatitis

Answer 127

Ongoing secondary hyperparathyroidism after correction of underlying renal disease, usually involving all 4 glands

Answer 128

Allow 12 months to elapse following transplant as most cases resolve Surgery required if parathyroid gland functioning autonomously – if found then excise otherwise total parathyroidectomy and re-implantation of part of the gland

Answer 129

Primary hypoparathyroidism – decreased PTH secretion secondary to gland failure (autoimmune, congenital) or other cause resulting in low calcium, high phosphate and is treated with Vitamin D.

Answer 130

Tetany – muscle twitching, cramping and spasm Perioral paraesthesia Trousseau’s sign – carpal spasm if the brachial artery occluded by inflating blood pressure cuff and maintaining pressure above systolic Chvostek’s sign – tapping over parotid causes facial muscles to twitch Chronic – depression and cataracts ECG prolonged QT interval

Answer 131

Target cells being insensitive to PTH due to abnormality in a G protein. Low calcium, high phosphate, high PTH. Associated with low IQ, short stature, shortened 4th and 5th metacarpals.

Answer 132

Diagnosis is made by measuring urinary cAMP and phosphate levels following an infusion of PTH. In hypoparathyroidism this will cause an increase in both cAMP and phosphate levels. In pseudohypoparathyroidism type I neither cAMP nor phosphate levels are increased whilst in pseudohypoparathyroidism type II only cAMP rises.

Answer 133

Similar phenotype to pseudohypoparathyroidism but normal biochemistry

Answer 134

Secondary hypoparathyroidism – due to radiation, surgery of the thyroid or parathyroid, hypomagnesaemia

Answer 135

Calcium supplements Vitamin D Synthetic PTH SC injection (this prevent hypercalciuria)

Answer 136

A Charcot joint is also commonly referred to as a neuropathic joint. It describes a joint which has become badly disrupted and damaged secondary to a loss of sensation. This is most commonly seen in diabetics. Clinical Features Less painful than would be expected given the degree of joint disruption due to the sensory neuropathy. The joint is typically swollen, red and warm