Endocrine and Metabolic Function

Question 1

Describe some of the common features of hypothyroidism.

Answer 1

Weight gain, low mood, intolerance of cold, tiredness, anorexia, poor libido, goitre, dry skin and hair, constipation, poor memory, arthralgia, myalgia

Question 2

Describe some of the clinical signs you may see in a patient presenting with hypothyroidism?

Answer 2

Peaches and cream complexion
Dry skin, thin hair
Loss of lateral 1/3 of eyebrow
Bradycardia
Proximal Myopathy, 
Slow relaxing reflexes

Question 3

List some of the main causes of Primary Hypothyroidism?

Answer 3

Atrophic (autoimmune) hypothyroidism
Hashimotos Thyroiditis
Post Partum Thyroiditis (transient, may be hypo or hyper)
Iatrogenic (following thryoidectomy or post radio-iodine therapy)

Question 4

Describe the Hypothalamic-Pituitary-Thyroid Axis

Answer 4

Hypothalamus detects with T4 is low
Secretes TRH (thyrotropin releasing hormone)
Which stimulates the anterior pituitary to secreate TSH (thyroid stimulating hormone)
Which stimulates the thyroid to secrete T3 and T4
Which has a negative feedback on the hypothalamus.

Question 5

In Primary Hypothyroidism, what will the TFTs show?

Answer 5

Low T4 and T3

High TSH

Question 6

In Secondary Hypothyroidism what will the TFTs show?

Answer 6

Low T3 and T4

Low TSH

Question 7

What are the common symptoms described in Hyperthyroidism?

Answer 7

Weight loss, increased appetite, irritability, tremor, heat intolerance, palpitations, diarrhoea, oligomennorrhoea, eye complaints

Question 8

Describe some of the clinical signs you may see in a patient presenting with Hyperthyroidism?

Answer 8

Tremor, Hyperkinesis, Proximal Myopathy, Tachycardia or AF, ward vasodilated peripheries, pretibial myxodema, thyroid acropachy

Question 9

Describe some of the common causes of Primary Hyperthyroidism.

Answer 9

Graves Disease (IgG binds to TSH receptors, stimulates)
Solitary Toxic Nodule
Toxic Multi-nodular Goitre
de Quervains Thyroiditis
Post Patrum Thyroiditis
Drug Induced Thyroiditis e.g. amiodarone, lithium

Question 10

In Primary Hyperythyroidism what will the TFTs show?

Answer 10

High T4 and T3

Low TSH

Question 11

In Secondary Hyperthyroidism what will the TFTs show?

Answer 11

High T4 and T3

High TSH

Question 12

List the ways in which Parathyroid Hormone (PTH) acts to increase plasma calcium.

Answer 12

Increase Osteoclastic Resorption of Bone (fast)
Increase Synthesis of Vit D in Kindey
Which will act to increase intestinal absorption of calcium (slow)
Increase renal tubular absorption of calcium
(Increases excretion of phosphate)

Question 13

How does HYPOparathyroidsism cause HYPOcalcaemia?

Answer 13

Hypoprarthyroisim = decreased function of the pararthyroid glands
Decreased PTH release
It is less able to act to increase serum calcium
Leads to hypocalcaemia.

Question 14

List some common causes of Hypocalcaemia

Answer 14

Hypoparathyroidism
Vitamin D Deficiency (less able to absorb from calcium from intestine)
CKD (increased phosphate levels)
Pseudohypoparathyroidism (resistance to PTH)
Drugs e.g. bisphosphonates, calcitonin, cisplatin

Question 15

Describe the clinical features of hypocalcaemia.

Answer 15

Neuromuscular Irritability and Neuropsychiatric Manifestations
e.g. parathesiae, circumoral numbness, cramps, anxiety and tetany
Followed by convulsions, laryngeal stridor and psychosis
Can also get prolonged QT interval on the ECG

Question 16

Describe Chvosteks Sign and when you would see it.

Answer 16

Seen in hypocalcaemia

Gentle tapping on the facial nerve causing twitching of the ipsilateral facial muscles

Question 17

Describe Trousseau’s Sign and when you would see it.

Answer 17

Seen in hypocalcaemia
Inflation of the sphygmomanometer cuff above systolic pressure for 3 minutes induces tetanic spasms of the fingers and wrist

Question 18

Describe the aetiology of Primary Hypoparathyroidism

Answer 18

Idiopathic (one of the rarer autoimmune disorders)
Surgical after neck exploration e.g. thyroidectomy
Syndromic e.g. DiGeorges Syndrome

Question 19

Describe DiGeorges Syndrome

Answer 19

Familial - Hypoparathyroidism is associated with intellectual impairement, cataracts and calcified basal ganglia.

Question 20

Describe how Primary HYPERparathyroidism causes HYPERcalcaemia

Answer 20

Parathyroid gland produces too much parathyroid hormone
Body is constantly stimulated to increase serum calcium
Leads to hypercalcaemia

Question 21

Describe some other common causes of Hypercalcaemia!

Answer 21

Malignancy e.g. Humoral Hypercalcaemia of Malignancy, Boney Mets, Myeloma
Excess Action of Vitamin D e.g. iatrogenic or self administered excess, granulomatous diseases, lymphoma
Drugs e.g. thiazide diuretics, vit D analogues,
Excessive calcium intake - milk-alkali syndrome
Familial Hypocalcuric Hypercalcaemia

Question 22

Describe the differences between primary, secondary and tertiary HYPERparathyroisim

Answer 22

PRIMARY

Hyperfunction of the parathyroid glands themselves (adenoma 85%, hyperplasia 15%, carcinoma

Question 23

Describe the clinical features of HYPERcalcaemia

Answer 23

STONES
Renal colic from kidney stones
BONES
Boney pain, locally destructive brown tumours
MOANS
Tiredness, malaise, depression
GROANS
Abdominal pain, constipation, anorexia
Get mild nephrogenic DI - nocturia

Question 24

Describe Humoural Hypercalcaemia of Malignancy

Answer 24

Mostly from squamous cell carcinomas
They secrete PTH related peptide (PTHrp)
Which acts as PTH would and increases serum calcium

Question 25

Other than humoral hypercalcaemia of malignancy, how else can malignancy causes hypercalcaemia?

Answer 25

``` Bone Erosion (20%) either from diffuse boney disease e.g. myeloma (IL-6 causes diffuse osteolysis) Rarer - ectopic PTH or vitamin D secretion by tumours ```

Question 26

In Primary HYPERparathyroidism what will blood tests show?

Answer 26

High PTH High Calcium Low Phosphate

Question 27

In Primary HYPOparathyroidism what will blood tests show?

Answer 27

Low PTH Low Calcium High Phosphate

Question 28

What is the treatment for severe acute hypercalcaemia?

Answer 28

FLUIDS (4-6L of saline on Day 1) | IV bisphosphonates

Question 29

Describe the treatment for Primary HYPERparathyroidism

Answer 29

If asymptomatic - conservative with regular monitoring (1/3 will go on to develop progressive hypercalcaemia, 2/3 will not so can avoid surgery in most, but must monitor regularly for the 1/3 that will need intervention) For those who are symptomatic surgery is indicated.

Question 30

What is the WHO definition for osteoporosis and osteopenia?

Answer 30

``` Osteoporosis = T-score >2.5 standard deviations below young healthy adult mean Osteopenia = 1-2.5 standard deviations below ```

Question 31

Describe the difference between T-score and Z-score in osteoprosis

Answer 31

``` T-score = BMD compared to race and sex matched peak adult BMD Z-score = BMD compared to age matched population ```

Question 32

What does the FRAX score calculate?

Answer 32

Calculates the 10 year # risk | Can be helpful when deciding whether to treat or not

Question 33

How would you diagnose osteoporosis?

Answer 33

DEXA scan is gold standard | N.B. Fragility fracture defines established osteoporosis.

Question 34

Describe the pharmacological and non-pharmacological treatment of osteoporosis.

Answer 34

Non-Pharmacological Adequate calcium and vitamin D intake, exercise (weight bearing), stop smoking, avoid excess alcohol, falls risk assessment and reduction of fall risk Pharmacological Bisphosphonates e.g. alendronate first line in most cases

Question 35

How do bisphosphonates work in osteoporosis?

Answer 35

Bond to hydroxyapatite and inhibit osteoclasts

Question 36

Describe the pathophysiology of osteomalacia.

Answer 36

Defective mineralisation of newly formed bone matrix

Question 37

Describe the pathophysiology of rickets (specifically how it is different from osteomalacia)

Answer 37

Defective mineralisation at the epiphyseal growth plate.

Question 38

Describe the most common cause of osteomalacia/rickets.

Answer 38

Deficient intake e.g. inadequate sun exposure or dietary intake/absorption of Vitamin D e.g. crohns, coeliac, gastrectomy

Question 39

Describe the difference between Vitamin D dependent Rickets Type I and II

Answer 39

Type I = due to deficiency of 1-alpha hydroxylase | Type II = defective vitamin D receptors

Question 40

Describe how patients with Osteomalacia/Rickets might present.

Answer 40

Asymptomatic - picked up on routine investigation When symptomatic - muscle weakness, widespread bone pain esp. on weight bearing, neonates - craniotabies, older children - bowing of legs or knock knees, waddling gait and difficulty climbing stairs/getting out chair

Question 41

How might osteomalacia appear on X-Ray?

Answer 41

Cupped Epipphysis Pseudofractures (Loosers Zones) Rachitic Rosary at chostochondral junction

Question 42

How do we treat osteomalacia/rickets?

Answer 42

Vitamin D and Calcium Supplementation

Question 43

What are the clinical features of Addisons Disease?

Answer 43

LEAN, TANNED, TIRED AND TEARFUL Weight loss and anorexia Pigementation - esp of new scars, palmar creases and buccal mucosa Tired - Malaise, weakness, postural hypotension and syncope, N&V, diarrhoea Tearful Depression,

Question 44

What is the main cause of Addisons Disease?

Answer 44

Autoimmune (>90% in UK)

Question 45

How might steroid therapy lead to Addisons Disease?

Answer 45

Long term glucocorticoid use can lead to suppression of the hypothalamic-pituitary-adrenal axis. if steroids are stopped suddenly, body may be unable to produce steroids leading to an Addisonian crisis.

Question 46

What test is used to diagnose Addisons Disease?

Answer 46

SYNACTHEN test Synthetic ACTH is given. In healthy individual who is given ACTH, body will respond by producing cortisol In Primary Addisons disease, adrenal glands not working so won't respond. Cortisol levels will not increase.

Question 47

What are the differences between Cushings syndrome and Cushings disease?

Answer 47

Cushings Syndrome = clinicak state of increased circulating glucocorticoid Cushings Disease = ACTH secreting pituitary adenoma

Question 48

What are the ACTH dependent clinical features of Cushings Syndrome?

Answer 48

Any pigmentation | ACTH-producing pituitary tumour may develop headaches, visual problems and galactorrhoea.

Question 49

What are the electrolyte abnormalities in Addisons Disease?

Answer 49

HYPERkalaemia | HYPOnatraemia

Question 50

Cushing's Syndrome has a 5 year mortality of >60% due to what complications?

Answer 50

Infection | Cardiovascular Complications

Question 51

What investigations would be done to diagnose Cushings Syndrome and then to find out cause?

Answer 51

CONFIRMATION Evening cortisol measurement - to confirm its high Dexamethasone Supression Test, healthy indivduals supress cortisol to

Question 52

Describe the pathophysiology of Primary Hyperaldosteronism.

Answer 52

Increased mineralocorticoid secretion from the adrenal cortex Leads to Sodium Retention - Hypertension (5-10% of all hypertension) Potassium Loss - Hypokalaemia and Alkalosis Dcreased renin release

Question 53

What is the aetiology of Primary Hyperaldosteronism?

Answer 53

``` Adrenal Adenomas (Conns Syndrome) (2/3) Bilateral Adrenal Hyperplasia (1/3) ```

Question 54

Describe the clinical features and aetiology of Kallman Syndrome.

Answer 54

Failure to start or complete puberty in males and females Accompanied by hypogonadsim and infertility Altered sense of smell - either absent or greatly reduced Caused by failure migration of neurones that release GnRH to the hypothalamus during embryonic developemnt

Question 55

Describe Klinefelters Syndrome

Answer 55

Two or more X chromosome in males The primary feature is sterility Symptoms may include weaker muscles, greater height, poor coordination, less body hair, smaller genitals, breast growth, and less interest in sex

Question 56

Describe the causes of Primary Testicular Failure

Answer 56

CONGENITAL Cryptochidism, chromosomal abnormality e.g. klinefelters ACQUIRED Testicular Torsion, Orchidectomy, Testicular Disease e.g. orchitis (mumps), cancer, chemotherpy/radiotherapy

Question 57

Describe the tumours/diseases associated with MEN-1 Syndrome

Answer 57

Pancreatic Islet Cell Tumours, Pituitary Adenomas, also Hyperparathyroidism (3Ps)

Question 58

Describe the tumours/disease associated with MEN2a and MEN2b

Answer 58

MEN2a = Medullary Thyroid Ca, Pheochromocytoma, Hyperparathyroidism (M, 2Ps) Men 2b = Medullary Thyroid Ca, Marfanoid habitus/mucosal neuroma, Pheochromocytoma (2Ms, P)

Question 59

Where is the majority of Sodium in the body, intracellular or extracellular?

Answer 59

Extracellular

Question 60

How do we examine and monitor someones fluid status?

Answer 60

EXAMINATION skin turgor, mucous membranes, JVP, auscultation of chest, oedema, ascites, MONITOR Fluid balance charts, weight change

Question 61

What are the causes of HYPOVOLAEMIC HYPONATRAEMIA?

Answer 61

LOSS OF SALT CONTAINING FLUIDS Renal loss - diuretics, mineralocorticoid deficiency GI loss - vomiting, diarrhoea Haemmorhage, burns POOR INTAKE Inadequate replacement e.g. NBM, critically unwell Environmental Deprivation

Question 62

What are the causes of HYPERVOLAEMIC HYPONATRAEMIA

Answer 62

Congestive cardiac failure Nephrotic Syndrome (hypoalbuminaemia) Cirrhosis Chronic Renal Failure

Question 63

What are the clinical features of HYPOnatraemia?

Answer 63

Spectrum | None --> Headache, Nausea, Vomiting, Lethargy --> Disorientation, seizures, cerebral oedema, coma, death

Question 64

What are the diagnostic criteria for SIADH?

Answer 64

``` Hyponatraemia Euvolaemia Concentrated Urine Dilute Plasma Normal adrenal and thyroid function ```

Question 65

Describe some of the causes of SIADH.

Answer 65

CNS tumour, trauma, infection, Guillain-Barré syndrome, multiple sclerosis, systemic lupus erythematosus vasculitis, intracranial haemorrhage, sinus thrombosis, AIDS, porphyria. TUMOURS SCLC, psotate, thymus, pancreas. lymphomas, leukaemias PULMONARY Pneumonia, TB, lung abscess, CF, mesothelioma, asthma OTHER Alcohol withdrawel, idiopathic, pain, endurance exercise DRUGS chlorpropramide, carbamazepine, selective serotonin reuptake inhibitor (SSRI) antidepressants, tricyclic antidepressants, lithium, MDMA/ecstasy, tramadol, haloperidol, vincristine, desmopressin, fluphenazine

Question 66

What is a common iatrogenic way of inducing hyponatraemia?

Answer 66

If 5% glucose is infused continuously without adding 0.9% saline, the glucose is quickly used rendering fluid hypotonic and causing hyponatraemia espescially in those going through physiological stress e.g. peri-operatively.

Question 67

List some common causes of HYPERnatraemia

Answer 67

``` FLUID LOSS WITHOUT WATER REPLACEMENT e.g. vomiting, diarrhoea DIABETES INSIPIDUS (nephrogenic or pituitary) expect if large volumes of urine OSMOTIC DIURESIS e.g. DKA, HONK IATROGENIC e.g. excessive saline ```

Question 68

Discuss the pathophyisology of pituitary vs nephrogenic diabetes insipidus.

Answer 68

Pituitary = Failure of ADH production by the pituitary | Nephrogenic - Failure of renal tubules to respond to ADH

Question 69

What test is used to diagnose Diabetes Insipidus?

Answer 69

Water Depriivation Test In patients with diabetes insipidus, the amount of fluid loss will not change. Whereas in a healthy patient restriction of water, would lead to secretion of ADH and more water rebasorbed, less excreted.

Question 70

What test is used to distinguish between nephrogenic diabetes insipidus and pituitary diabetes insipidus?

Answer 70

``` Give Desmopressin (a synthetic vasopressin) Central DI - patients will respond Nephrogenic DI - kidneys cannot respond to ADH and therefore there will be no change. ```

Question 71

Where in the body is potassium mostly found?

Answer 71

Intra-cellular Compartment

Question 72

What things influence potassium influx INTO cells?

Answer 72

Insulin Beta-Adrenergic Stimulation Alkalosis Theophylines

Question 73

What things influence potassium efflux OUT of cells?

Answer 73

Alpha-Adrenergic Stimulation Acidosis Cell Damage or Cell Death (results in massive K+ release) Strenuous Exercise

Question 74

Describe the relationship between pH and potassium

Answer 74

ACIDOSIS + HYPERKALAEMIA | ALKALOSIS + HYPOKALAEMIA

Question 75

List the main causes of Hypokalaemia

Answer 75

Increased Renal Excretion i.e. Diuretics or Renal Pathology e.g. tubular disorders like Gitelmans Increased Aldosterone Secretion (pump out K+ for ever Na+ pumped in) Exogenous Mineralocorticoid Reduced Intake of K+ e.g. IV fluids without potassium, dietary deficiency Redistribution into cells e.g. acute MI (beta adrenergic stimultation), insuling treatment in DKA, alkalosis GI Losses - vomiting, severe diarrhoea, laxative abuse

Question 76

What is the relationship between HYPOkalaemia and Digoxin

Answer 76

You get a predisposition to digoxin toxicity, by increase binding of digoxin to cardiac cells potentiating its effects and decreasing its clearance

Question 77

How does insulin increase potassium uptake into cells?

Answer 77

Insertion of GLUT 4 into membrane which increases the activity of the Na+/K+ ATPase (2 potassium pumped in for every 3 sodium pumped out)

Question 78

How should hypokalaemia be managed?

Answer 78

Treat underlying cause if there is one. In most cases withdrawal of causative factors and oral potassium supplements will suffice IV potassium only needed in conditions such as cardiac arrythmias, muscle weakness or severe DKA Failure to correct could be due to concurrent hypomagnesaemia - serum magnsium should be checked and any deficiency corrected

Question 79

List some causes of Hyperkalaemia

Answer 79

INCREASED RELEASE FROM CELLS e.g. acidosis, DKA, rhabdomyolysis, tymour lysis syndrome, vigourous exercise (alpha-adrengeric - transient) DECREASED EXCRETION AKI, drugs e.g. K+ sparing diuretics, ACE inhibitors/ARBs,, Addisons Disease, INCREASED POTASSIUM Iatrogenic potassium replacement, blood transfusion

Question 80

List the correct order of ECG changes in hyperkalaemia

Answer 80

Tented T waves Reduced P wave Wide QRS Sine Wave

Question 81

List the correct order of ECG changes in hypokalaemia

Answer 81

T wave flattening ST depresson T wave inversion Increased P waves

Question 82

Describe the emergency treatment for Hyperkalaemia

Answer 82

ECG monitor and IV access PROTECT MYOCARDIUM - IV calcium gluconate Then need to drive K+ into cells Insulin + Glucose to prevent hypo Then later deplete total body K+ with polystyrene sulphonate resins All of the above are buying time to remove the underlying cause, or to prepare for dialysis which is the definitive treatment for removal of K+ in renal failure.

Question 83

What two things are produced by the posterior pituitary (everything else is anterior)

Answer 83

ADH/Vasopressin | Oxytocin

Question 84

Describe the mass effect symptoms of a pituitary adenoma

Answer 84

Headaches and nausea (raised ICP) | Visual Disturbance - classical bitemporal hemianopia

Question 85

Describe Pituitary Apoplexy and its urgen treatment

Answer 85

Infarction/Haemorrhage of the anterior pituitary Patients present with - acute headache, collapse, sudden visual loss or death. Fluid resuscitation and IV steroids - life saving

Question 86

Why do you only get glucocorticoid deficiency in secondary ACTH deficiency?

Answer 86

Because mineralocorticoid release is principally controlled by the renin-angiotensin system. Therefore, is not effected.

Question 87

By looking at the patient, how could you determine whether they had primary (addisons) ,or secondary glucocortcoid deficiency?.

Answer 87

Primary - will be pigmented as pituitary will secrete ACTH | Secondary - not pigmented as pituitary is not producing ACTH.

Question 88

Why is it important prior to surgery to remove a TSH-oma, to make patient euthyroid?

Answer 88

As surgery of hyperthyroid patients have increased morbidity and mortality

Question 89

Why do women with prolactinomas tend to present earlier than men?

Answer 89

For women galactorrhoea occurs early and is an alarming feature, whereas for men it is a late occurring feature. Therefore, men will often present with mass effect from large tumours.

Question 90

How are prolactinomas managed?

Answer 90

Unique - medical treatement rather than surgical treatment. Give dopamine antagonists e.g. cabergoline or bromocriptine. They shrink adenoma as dopamine inhibits prolactin release

Question 91

Describe some of the clinical features of acromegaly

Answer 91

frontal bossing, coarse facial features, increased interdental spacing, enlarged hands and feet, sweating, organomegaly, carpal tunnel syndrome, osteoarthritis, visual field defects (macroadenoma), excess of neoplasms e.g. colon, breast, obstructive sleep apnoea, hypertension, cardiovascular disease, impraired glucose tolerance --> diabetes.

Question 92

What tests are used to diagnose acromegaly?

Answer 92

Elevated IGF-1 levels Failure of GH levels to supress following OGTT Imaging - often pituitary macroadenoma

Question 93

What sign on CT would make you suspiscious of a central diabetes insipidus?

Answer 93

Absent posterior pituitary bright spot | ADH vesicles in posterior pituitary shine bright

Question 94

Describe the clinical features of diabetes insipidus

Answer 94

``` Polyuria (3-20L/day) Nocturia Polydipsia Dehydration Hypernatraemia ```

Question 95

Describe what MODY is?

Answer 95

A collection of single gene defects affecting beta cell function

Question 96

Describe key points of glucokinase variant of MODY

Answer 96

Glucokinase - receptor involved in glucose signallling to beta cell. (Chr 7) Mutation means increased threshold for normal insulin secretion and persistantly high glucose It is present from birth (babies often have low birthweight), there is little deterioration with age and microvascular complications are rare.

Question 97

Describe the key points of HNF1a variant of MODY

Answer 97

HNf1a = transcription factor in beta cell (Chr 12) Most common form Symptoms present in late teens/early 20s Progressive hyperglycemia and miscrovascular complications are frequent Very sensitive to treatment with sulphonylureas.

Question 98

Describe key points of HNF1b variant of MODY

Answer 98

HNF1b = transcription factor in beta cell (Chr 17) Presents in Teens/20s Can get microvascular complications frequently Associated with renal cysts, infertility, gout

Question 99

Describe the different problems in transient and permanent diabetes of the newborn

Answer 99

TRANSIENT Due to methylation on Chr6. Usually resolves by 3 months. approx 50% relapse in teens. PERMANENT Insulin Channel permanently depolarised by activating mutation. 20% have developmental delay and epilespy as well as diabetes.