Endocrine and Metabolic Function Flashcards
Describe some of the common features of hypothyroidism.
Weight gain, low mood, intolerance of cold, tiredness, anorexia, poor libido, goitre, dry skin and hair, constipation, poor memory, arthralgia, myalgia
Describe some of the clinical signs you may see in a patient presenting with hypothyroidism?
Peaches and cream complexion Dry skin, thin hair Loss of lateral 1/3 of eyebrow Bradycardia Proximal Myopathy, Slow relaxing reflexes
List some of the main causes of Primary Hypothyroidism?
Atrophic (autoimmune) hypothyroidism
Hashimotos Thyroiditis
Post Partum Thyroiditis (transient, may be hypo or hyper)
Iatrogenic (following thryoidectomy or post radio-iodine therapy)
Describe the Hypothalamic-Pituitary-Thyroid Axis
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.
In Primary Hypothyroidism, what will the TFTs show?
Low T4 and T3
High TSH
In Secondary Hypothyroidism what will the TFTs show?
Low T3 and T4
Low TSH
What are the common symptoms described in Hyperthyroidism?
Weight loss, increased appetite, irritability, tremor, heat intolerance, palpitations, diarrhoea, oligomennorrhoea, eye complaints
Describe some of the clinical signs you may see in a patient presenting with Hyperthyroidism?
Tremor, Hyperkinesis, Proximal Myopathy, Tachycardia or AF, ward vasodilated peripheries, pretibial myxodema, thyroid acropachy
Describe some of the common causes of Primary Hyperthyroidism.
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
In Primary Hyperythyroidism what will the TFTs show?
High T4 and T3
Low TSH
In Secondary Hyperthyroidism what will the TFTs show?
High T4 and T3
High TSH
List the ways in which Parathyroid Hormone (PTH) acts to increase plasma calcium.
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)
How does HYPOparathyroidsism cause HYPOcalcaemia?
Hypoprarthyroisim = decreased function of the pararthyroid glands
Decreased PTH release
It is less able to act to increase serum calcium
Leads to hypocalcaemia.
List some common causes of Hypocalcaemia
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
Describe the clinical features of hypocalcaemia.
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
Describe Chvosteks Sign and when you would see it.
Seen in hypocalcaemia
Gentle tapping on the facial nerve causing twitching of the ipsilateral facial muscles
Describe Trousseau’s Sign and when you would see it.
Seen in hypocalcaemia
Inflation of the sphygmomanometer cuff above systolic pressure for 3 minutes induces tetanic spasms of the fingers and wrist
Describe the aetiology of Primary Hypoparathyroidism
Idiopathic (one of the rarer autoimmune disorders)
Surgical after neck exploration e.g. thyroidectomy
Syndromic e.g. DiGeorges Syndrome
Describe DiGeorges Syndrome
Familial - Hypoparathyroidism is associated with intellectual impairement, cataracts and calcified basal ganglia.
Describe how Primary HYPERparathyroidism causes HYPERcalcaemia
Parathyroid gland produces too much parathyroid hormone
Body is constantly stimulated to increase serum calcium
Leads to hypercalcaemia
Describe some other common causes of Hypercalcaemia!
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
Describe the differences between primary, secondary and tertiary HYPERparathyroisim
PRIMARY
Hyperfunction of the parathyroid glands themselves (adenoma 85%, hyperplasia 15%, carcinoma
Describe the clinical features of HYPERcalcaemia
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
Describe Humoural Hypercalcaemia of Malignancy
Mostly from squamous cell carcinomas
They secrete PTH related peptide (PTHrp)
Which acts as PTH would and increases serum calcium
Other than humoral hypercalcaemia of malignancy, how else can malignancy causes hypercalcaemia?
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
In Primary HYPERparathyroidism what will blood tests show?
High PTH
High Calcium
Low Phosphate
In Primary HYPOparathyroidism what will blood tests show?
Low PTH
Low Calcium
High Phosphate
What is the treatment for severe acute hypercalcaemia?
FLUIDS (4-6L of saline on Day 1)
IV bisphosphonates
Describe the treatment for Primary HYPERparathyroidism
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.
What is the WHO definition for osteoporosis and osteopenia?
Osteoporosis = T-score >2.5 standard deviations below young healthy adult mean Osteopenia = 1-2.5 standard deviations below
Describe the difference between T-score and Z-score in osteoprosis
T-score = BMD compared to race and sex matched peak adult BMD Z-score = BMD compared to age matched population
What does the FRAX score calculate?
Calculates the 10 year # risk
Can be helpful when deciding whether to treat or not
How would you diagnose osteoporosis?
DEXA scan is gold standard
N.B. Fragility fracture defines established osteoporosis.
Describe the pharmacological and non-pharmacological treatment of osteoporosis.
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
How do bisphosphonates work in osteoporosis?
Bond to hydroxyapatite and inhibit osteoclasts
Describe the pathophysiology of osteomalacia.
Defective mineralisation of newly formed bone matrix
Describe the pathophysiology of rickets (specifically how it is different from osteomalacia)
Defective mineralisation at the epiphyseal growth plate.
Describe the most common cause of osteomalacia/rickets.
Deficient intake e.g. inadequate sun exposure or dietary intake/absorption of Vitamin D e.g. crohns, coeliac, gastrectomy
Describe the difference between Vitamin D dependent Rickets Type I and II
Type I = due to deficiency of 1-alpha hydroxylase
Type II = defective vitamin D receptors
Describe how patients with Osteomalacia/Rickets might present.
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
How might osteomalacia appear on X-Ray?
Cupped Epipphysis
Pseudofractures (Loosers Zones)
Rachitic Rosary at chostochondral junction
How do we treat osteomalacia/rickets?
Vitamin D and Calcium Supplementation
What are the clinical features of Addisons Disease?
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,
What is the main cause of Addisons Disease?
Autoimmune (>90% in UK)
How might steroid therapy lead to Addisons Disease?
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.
What test is used to diagnose Addisons Disease?
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.
What are the differences between Cushings syndrome and Cushings disease?
Cushings Syndrome = clinicak state of increased circulating glucocorticoid
Cushings Disease = ACTH secreting pituitary adenoma
What are the ACTH dependent clinical features of Cushings Syndrome?
Any pigmentation
ACTH-producing pituitary tumour may develop headaches, visual problems and galactorrhoea.
What are the electrolyte abnormalities in Addisons Disease?
HYPERkalaemia
HYPOnatraemia
Cushing’s Syndrome has a 5 year mortality of >60% due to what complications?
Infection
Cardiovascular Complications
What investigations would be done to diagnose Cushings Syndrome and then to find out cause?
CONFIRMATION
Evening cortisol measurement - to confirm its high
Dexamethasone Supression Test, healthy indivduals supress cortisol to
Describe the pathophysiology of Primary Hyperaldosteronism.
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
What is the aetiology of Primary Hyperaldosteronism?
Adrenal Adenomas (Conns Syndrome) (2/3) Bilateral Adrenal Hyperplasia (1/3)
Describe the clinical features and aetiology of Kallman Syndrome.
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
Describe Klinefelters Syndrome
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
Describe the causes of Primary Testicular Failure
CONGENITAL
Cryptochidism, chromosomal abnormality e.g. klinefelters
ACQUIRED
Testicular Torsion, Orchidectomy, Testicular Disease e.g. orchitis (mumps), cancer, chemotherpy/radiotherapy
Describe the tumours/diseases associated with MEN-1 Syndrome
Pancreatic Islet Cell Tumours, Pituitary Adenomas,
also Hyperparathyroidism
(3Ps)
Describe the tumours/disease associated with MEN2a and MEN2b
MEN2a = Medullary Thyroid Ca, Pheochromocytoma, Hyperparathyroidism (M, 2Ps)
Men 2b = Medullary Thyroid Ca, Marfanoid habitus/mucosal neuroma, Pheochromocytoma (2Ms, P)
Where is the majority of Sodium in the body, intracellular or extracellular?
Extracellular
How do we examine and monitor someones fluid status?
EXAMINATION
skin turgor, mucous membranes, JVP, auscultation of chest, oedema, ascites,
MONITOR
Fluid balance charts, weight change
What are the causes of HYPOVOLAEMIC HYPONATRAEMIA?
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
What are the causes of HYPERVOLAEMIC HYPONATRAEMIA
Congestive cardiac failure
Nephrotic Syndrome (hypoalbuminaemia)
Cirrhosis
Chronic Renal Failure
What are the clinical features of HYPOnatraemia?
Spectrum
None –> Headache, Nausea, Vomiting, Lethargy –> Disorientation, seizures, cerebral oedema, coma, death
What are the diagnostic criteria for SIADH?
Hyponatraemia Euvolaemia Concentrated Urine Dilute Plasma Normal adrenal and thyroid function
Describe some of the causes of SIADH.
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
What is a common iatrogenic way of inducing hyponatraemia?
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.
List some common causes of HYPERnatraemia
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
Discuss the pathophyisology of pituitary vs nephrogenic diabetes insipidus.
Pituitary = Failure of ADH production by the pituitary
Nephrogenic - Failure of renal tubules to respond to ADH
What test is used to diagnose Diabetes Insipidus?
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.
What test is used to distinguish between nephrogenic diabetes insipidus and pituitary diabetes insipidus?
Give Desmopressin (a synthetic vasopressin) Central DI - patients will respond Nephrogenic DI - kidneys cannot respond to ADH and therefore there will be no change.
Where in the body is potassium mostly found?
Intra-cellular Compartment
What things influence potassium influx INTO cells?
Insulin
Beta-Adrenergic Stimulation
Alkalosis
Theophylines
What things influence potassium efflux OUT of cells?
Alpha-Adrenergic Stimulation
Acidosis
Cell Damage or Cell Death (results in massive K+ release)
Strenuous Exercise
Describe the relationship between pH and potassium
ACIDOSIS + HYPERKALAEMIA
ALKALOSIS + HYPOKALAEMIA
List the main causes of Hypokalaemia
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
What is the relationship between HYPOkalaemia and Digoxin
You get a predisposition to digoxin toxicity, by increase binding of digoxin to cardiac cells potentiating its effects and decreasing its clearance
How does insulin increase potassium uptake into cells?
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)
How should hypokalaemia be managed?
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
List some causes of Hyperkalaemia
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
List the correct order of ECG changes in hyperkalaemia
Tented T waves
Reduced P wave
Wide QRS
Sine Wave
List the correct order of ECG changes in hypokalaemia
T wave flattening
ST depresson
T wave inversion
Increased P waves
Describe the emergency treatment for Hyperkalaemia
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.
What two things are produced by the posterior pituitary (everything else is anterior)
ADH/Vasopressin
Oxytocin
Describe the mass effect symptoms of a pituitary adenoma
Headaches and nausea (raised ICP)
Visual Disturbance - classical bitemporal hemianopia
Describe Pituitary Apoplexy and its urgen treatment
Infarction/Haemorrhage of the anterior pituitary
Patients present with - acute headache, collapse, sudden visual loss or death.
Fluid resuscitation and IV steroids - life saving
Why do you only get glucocorticoid deficiency in secondary ACTH deficiency?
Because mineralocorticoid release is principally controlled by the renin-angiotensin system. Therefore, is not effected.
By looking at the patient, how could you determine whether they had primary (addisons) ,or secondary glucocortcoid deficiency?.
Primary - will be pigmented as pituitary will secrete ACTH
Secondary - not pigmented as pituitary is not producing ACTH.
Why is it important prior to surgery to remove a TSH-oma, to make patient euthyroid?
As surgery of hyperthyroid patients have increased morbidity and mortality
Why do women with prolactinomas tend to present earlier than men?
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.
How are prolactinomas managed?
Unique - medical treatement rather than surgical treatment. Give dopamine antagonists e.g. cabergoline or bromocriptine.
They shrink adenoma as dopamine inhibits prolactin release
Describe some of the clinical features of acromegaly
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.
What tests are used to diagnose acromegaly?
Elevated IGF-1 levels
Failure of GH levels to supress following OGTT
Imaging - often pituitary macroadenoma
What sign on CT would make you suspiscious of a central diabetes insipidus?
Absent posterior pituitary bright spot
ADH vesicles in posterior pituitary shine bright
Describe the clinical features of diabetes insipidus
Polyuria (3-20L/day) Nocturia Polydipsia Dehydration Hypernatraemia
Describe what MODY is?
A collection of single gene defects affecting beta cell function
Describe key points of glucokinase variant of MODY
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.
Describe the key points of HNF1a variant of MODY
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.
Describe key points of HNF1b variant of MODY
HNF1b = transcription factor in beta cell (Chr 17)
Presents in Teens/20s
Can get microvascular complications frequently
Associated with renal cysts, infertility, gout
Describe the different problems in transient and permanent diabetes of the newborn
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.
