Endocrinology Flashcards
Define T1DM
Autoimmune destruction of pancreatic B-cells leading to absolute insulin deficiency
T4 Hypersensitivity reaction
T1DM epidaemiology
Young
Lean
Northern European descent (Finland!)
Risk factors for T1DM
HLADR2 DQ3
HLADR4 DQ8
Other autoimmune condition
Environmental infection - could be a trigger!
Pathophysiology for T1DM
Autoimmune destruction of B-cells in islet of langerhan leads to absolute deficiency in insulin production —>
Hyperglycaemia and lower cellular glucose —>
Increased lipolysis & gluconeogenesis.
Insulin helps draw potassium in along with glucose [therefore, Hyperkalaemia even though full body k+ is low]
Signs/symptoms of T1DM
Young, lean
Polyuria, polydipsia, polyphagia
Weight loss
Glucosuria (+/- signs of ketogenesis)
When can T1DM Sx be diagnostic
When signs and symptoms are present with diabetes complications
Investigations and diagnosis for T1DM
Fasting blood glucose (FBG): < 7.0 mmol/L = normal
> 7.0 mmol/L = T1DM
Random blood glucose (RBG): < 11.1 mmol/L = normal
> 11.1 mmol/L = T1DM
HBA1C: > 48 mmol/L or 6.5% = T1DM
OGTT: Give 75g fast acting glucose… then measure blood glucose 2hrs later… > 11.1 mmol/L diagnostic
Prediabetic values for T1DM
None - no pre-diabetes
No lifestyle modification will affect this type of diabetes from developing.
Treatment for T1DM
Basal Bolus Insulin
Basal = longer acting, maintain stable insulin level throughout the day
Bolus = faster acting, 30 mins preprandial (before meal) to give “insulin spike”
4 types of insulin
Rapid - Novorapid, Aspart
Short - regular insulin
Intermediate - NPH
Long - detemir
The main complication for T1DM
Diabetes ketoacidosis
Define diabetes ketoacidosis (DKA)
Occurs from poorly managed T1DM
Or from infection/illness
Characteristic Px = 10y/o presents to A&E with severe dehydration + Hx of T1DM
Pathophysiology of diabetes ketoacidosis
Absolute insulin deficiency leads to unrestrained lipolysis + gluconeogenesis
You get so much gluconeogenesis (not all glucose is usable) therefore, converted to ketone bodies.
Ketone bodies = acidic therefore, increased concentration -> ketoacidosis
Signs or symptoms of DKA
T1DM Sx +
Kussmaul breathing (deep laboured breaths, to blow off CO2 - as compensation)
Pear drop breath (fruity ketone breath smell)
Reduced tissue turgor, hypotension + tachycardia
Investigation and diagnosis for DKA
Bloods:
Ketones > 3mmol/L
Hyperglycaemic > 11.1 mmol/L (RPG)
Acidosis (metabolic) < 7.3 pH or <15 mmol HCO3-
(These 3 = diagnostic)
+ Ketonuria, Glycosuria, Hyperkalaemia
Treatment for DKA
ABCDE (emergency)
1st line ALWAYS fluids - in most patients because of dehydration first
Then
Insulin (+ glucose, prevent hypoglycaemia)
( + potassium, replenish K+ stores)
Define T2DM
Peripheral insulin resistance with partial insulin deficiency
(Cholesterol/lipid and Beta amyloid deposits in pancreas)
T2DM epidaemiology
Presents later in life (30+)
M>F
Cause of T1DM
Autoimmunity
Genetics
Idiopathic
LADA —> Latent Autoimmune Diabetes in Adults
What is LADA
Latent Autoimmune Diabetes in adults
It’s a slower variant of T1DM… so… slower progression of insulin deficiency.
Harder to differentiate between it and T2DM
What is MODY
Maturity onset diabetes of the young
It is rare autoimmune condition similar to T2DM but presents in youth rather than older age.
TREATMENT - sulfonylurea (gliclizide)
Risk factors for T2DM
Genetic link (fHx - much stronger than HLA link in T1DM)
Smoking
Obesity
Hypertension
Sedentary lifestyle
What is T2DM a risk factor for…
Hypertension
Silent MI
Nephrotic syndrome
CKD
Pathophysiology for T2DM
Repeated exposure could lead to peripheral insulin resistance (i.e malfunctional insulin intracellular activation pathway)
Therefore, decreased GLUT-4 expression
Also
+ minor destruction of pancreatic islets (amyloid + cholesterol/lipid deposits)
All leading to hyperglycaemia with increased insulin demand from a depleted B cell population
Signs / symptoms for T2DM
Obesity
Hypertensive older Px
Polydipsia, polyuria + nocturia, glycosuria
Acanthosis nigracans; dark pigmented skin folds (sign of severe insulin resistance)
Investigation and diagnosis of T2DM
Same as T1DM
FPG > 7 mmol/L, RBG > 11.1 mmol/L, HBA1C > 48 or 6.5%
However, patient in T2DM could have a pre-diabetic state
Diagnosing prediabetic state
Diagnosed for T2DM, you have…
Impaired glucose tolerance
Plasma glucose after 2hrs 7.8 - 11.1 mmol/L (OGTT)
Impaired fasting glucose
Blood glucose 6.1 - 6.9 mmol/L
HBA1C
Between 42 - 47 mmol/mol
Treatment for pre diabetics
Lifestyle change / Modify risk factors
Like diet and exercise
Treatment for T2DM
1st line: Metformin
2nd line (if HBA1C is > 58 or 7.5%): add another drug Sulfonylurea - Gliclizide
3rd line: if persistently high, add another drug DPP-4 inhibitor or SGLT-2 inhibitor
4th line: last resort consider giving insulin
What type of drug is Metformin
Biguanide - increases insulin sensitivity and decreases liver production of glucose.
Weight neutral
Does NOT typically cause hypoglycaemia
Side effects:
Lactic acidosis
Diarrhoea and abdominal pain
Type of drug is Gliclazide
Sulfonyluria - stimulate insulin release from the pancreas
Weight gain
CAN cause hypoglycaemia
Increased risk of MI
Main complication of T2DM
HHS
Hyperosmolar hyperglycaemic state
Explain what to do in HHS
Often precipitated with infection - pneumonia
Pathophysiology - excessive hepatic gluconeogenesis (not totally insulin deficient, therefore you don’t get ketosis) - instead glucose = osmotically active so the excess glucose causes Hyperosmolar blood
Sx - severe T2DM, REDUCED CONCIOUSNESS
Dx - heavy glycosuria, increased plasma osmolality (> 300 mmol/L) with hyperglycaemia - NO ketonuria / hyperketonemia
Tx - first INSULIN (+ glucose, K+)
Then give fluids - 0.9% saline
Could give LMWH - anticoagulant as they have thicker blood.
What are the complications of DM
Macro-vascular
Cardiovascular (MI)
Cerebrovascular (Ischaemic stroke)
Peripheral arterial (PVD)
Micro-vascular
Retinopathy
Neuropathy (charat foot)
Nephropathy (nephrotic syndrome / CKD)
Define hypoglycaemia
Abnormally low blood glucose
< 3.3 mmol/L
Signs/symptoms of someone who is hypoglycaemic
Reduced conciousness
Dizziness
Syncope
Treatment for hypoglycaemia
IV glucose, if no IV acces give
IM glucagon
What could cause someone to be hypoglycaemic
Could be a result of diabetes drugs - sulfonylureas / insulin
In non-diabetics - diet, liver failure or Addison’s
What are the causes of hyperthyroidism
Graves (most common)
Toxic multinodular goitre - nodules secreting thyroid hormones
Toxic adenoma (solitary toxic thyroid nodule)
Ectopic TSH secretion - from ovarian Teratoma
De quervains thyroiditis - swollen, red, tender goitre (could be post viral infection)
Hyperthyroidism epidaemiology
F > M
Define hyperthyroidism
Hyperthyroidism is where there is over-production of thyroid hormone by the thyroid gland.
AKA thyrotoxicosis
Primary hyperthyroidism is due to thyroid pathology
Secondary hyperthyroidism is the condition where the thyroid is producing excessive t3/t4 as a result of overstimulation by TSH. The pathology is in the hypothalamus or pituitary
Pathophysiology of hyperthyroidism
In most common case: TSH-R autoantibodies
Mimic TSH and stimulate the TSH receptors on the thyroid.
I.e. Grave’s disease (an autoimmune condition).
Remember the role of t3/t4 is metabolism… so in excess the symptoms of metabolism are heightened
Symptoms of hyperthyroidism
Weight loss + hyperphagia
Anxiety
Heat intolerance
Diarrhoea
Oligomenorrhoea
Signs of hyperthyroidism
Tachycardia
Goitre (usually diffused, unless Toxic M.G)
Muscle wasting
Fine tremor
Specific to graves… (triad of…)
Exophthalmos (opthalmopathy)
Pretibial myxoedema (dermopathy)
Acropachy (clubbing + swelling + new bone formation)
Investigation / diagnosis of hyperthyroidism
TFTs: Low TSH… high T3/4 = primary hyperthyroidism
High TSH… high T3/4 = secondary hyperthyroidism
Low TSH… normal T3/4 = sub-clinical hyperthyroidism
High TSH… normal T3/4 = sub-clinical hypothyroidism
Other tests:
Blood levels: TSH-R autoantibodies +ve in Grave’s
In 80% of cases anti-TPO Ab’s (more in hypothyroidism though)
Thyroid UltraSound Scan: differentiates diffused from toxic MG
1st line treatment for hyperthyroidism
Carbimazole
When is carbimazole Contraindicated for hyperthyroidism
In pregnancy
Give propylthiouracil
Use “block and replace” effect… dose is sufficient to block all production and the patient takes levothyroxine titrated to effect
Side effects of carbimazole
Agranulocytosis
Presents as a sore throat
Treatment for hyperthyroidism
1st line = Cabimazole
+ propranolol (beta blocker for symptomatic relief)
2nd line = propylthiouracil
Could give radioactive iodine (definitive - destroys excess thyroid tissue) - contraindicated: pregnancy
Last resort = surgery (thyroidectomy)
Complications for hyperthyroidism
Thyroid storm (main comp)
Heart failure - because increased workload on heart due to increased metabolism
Osteoporosis - increased metabolism of the bone (increased bone resorption)
What is thyroid storm
Rapid deterioration of thyrotoxicosis and have extremely high levels of T3/4
Systemic decompensation:
A Fib
Hypertension
Coma
Treatment: propylthiouracil + KI (high dose)
Signs related to Graves’ disease
Exophthalmos - build up glycosaminoglycan + inflammation and swelling around the eye causes it to bulge
Pretibial myxoedema
Acropachy
Role of triiodothyronine (t3)
Speeds up basal metabolic rate
Cells produce more proteins & burn more energy (using lipids and sugar)
Increases cardiac output
Increases bone resorption
Activates sympathetic nervous system
Remember most thyroxine converts into t3 to produce an effect
Epidaemiology of hypothyroidism
F > M
Ageing
Postpartum
Cause of hypothyroidism (primary)
Developed world:
Most common = Hashimoto’s thyroiditis
Developing world + worldwide:
Iodine deficiency
Drugs - Amiodarone (can also cause hyperthyroidism) / lithium
De quervains (progressed)
Treatment for hyperthyroidism- surgery / radioactive iodine / too much carbimazole/propylthiouracil
Define hypothyroidism
Hypothyroidism is the term used to describe an inadequate output of thyroid hormones by the thyroid gland.
Primary hypothyroidism - inability of the thyroid gland to produce hormones
Secondary hypothyroidism - pituitary / hypothalamus is failing to stimulate the the thyroid gland by not secreting TSH
Explain Hashimoto’s thyroiditis and what disease does it cause
Most common cause of hypothyroidism
An autoimmune inflammation of the thyroid gland.
Associated with Antithyroid peroxidase (anti-TPO) antibodies
And antithyroglobulin antibodies.
Initially it causes a goitre and eventually leads to atrophy of thyroid gland.
Causes of secondary hypothyroidism
Hypopituitarism
-tumour
-radiation
-surgery
-infection
Symptoms of Px with hypothyroidism
Weight gain
Cold intolerance
Constipated
Lethargy
Menorrhagia
Signs of Px with hypothyroidism
Bradycardia
Slow reflexes
Goitre (if Hashimoto’s / iodine deficient)
Myxoedema
Investigations / diagnosis of hypothyroidism
TFT’s:
High TSH… Low T3/4 = primary hypothyroidism
Low TSH… Low t3/4 = secondary hypothyroidism
High TSH… Normal T3/4 = sub-clinical hypothyroidism
Anti-TPO / Anti-TGA Ab’s
May be anaemic ( can be all types; microcytic / Normacytic normachromic / Macrocytic)
Treatment for hypothyroidism
Levothyroxine (T4) - careful with dose, can cause iatrogenic hyperthyroidism
and the dose is titrated until TSH levels are normal
What is the complication of hypothyroidism
Myxoedema coma
Often infection induced
Rapid decrease in thyroid hormones
Px seen as: hypothermic, loss of consciousness, heart failure
Treatment: levothyroxine, ABx + hydrocortisone (until adrenal insufficiency hasn’t been ruled out
What types of thyroid carcinomas are there
Papillary (most common - 70%)
Follicular (25%)
Anaplastic (worst prognosis) - metastasises the most
Medullary cell carcinoma
What are the most common sites of metastases for thyroid cancers
Remember as LBLB:
LUNG - 50%
BONE - 30%
LIVER - 10%
BRAIN - 5%
Signs / symptoms of patient with thyroid carcinoma
Hard + irregular thyroid nodules
Could have hoarse voice (if theres compression of recurrent laryngeal nerve)
Other signs of carcinomas like… sudden weight loss, bleeding
How to diagnose thyroid carcinoma
Fine needle aspiration biopsy
TFTs
Thyroid USS
Treatment for thyroid carcinoma
For papillary + follicular:
Thyroidectomy or radiotherapy
For anaplastic:
Mainly palliative care
Remember any removal of thyroid will need lifelong hormone replacement - levothyroxine
Define Cushing disease and syndrome
Cushings disease = increased cortisol levels due to pituitary adenoma
Cushings syndrome = increased cortisol level from any cause
Note: pseudo-Cushing’s is due to alcohol… this resolves in 1-3 weeks.
Role of cortisol
Free coritisol is part of the circadian rhythm… peaks in morning, reduces by night
The ‘stress’ hormone:
Increased gluconeogenesis, proteolysis and lipolysis… increased glucose
Increased sensitivity for catecholamines (sympathetic innervation) in peripheries… narrowed blood vessels
Dampens immune response, so reduced inflammatory mediators and t-lymphocyte proliferation.
Inhibits GnRH decreased ovarian and testicular function.
Causes of Cushing’s syndrome
ACTH DEPENDENT
Most common = Cushing disease (pituitary adenoma)
Ectopic ACTH (SCLC)
ACTH INDEPENDENT
Most common OVERALL cause = Iatrogenic (steroid use)
Adrenal adenoma
Pathophysiology of Cushing’s
CRH—>ACTH—> Cortisol (in a -ve feedback loop) - this feedback loop either doesn’t work or have increased secretion of cortisol independent to the loop… causing Sx
Signs and symptoms for Cushing’s syndrome
Moon face, central obesity, buffalo hump
Abdominal striae
Peripheral limb weakness and muscle atrophy
Osteoporosis
Plethoric complexion
Susceptible to infection
Investigation / diagnosis for Cushing’s
Rule out oral steroids - if on steroids… ween them off
Random serum cortisol test if high then measure cortisol at 12am (should be low here but if high then thats abnormal)
If first line +ve, then measure plasma ACTH
High = ACTH dependant —> look for C.disease on pituitary MRI
Low = non-ACTH dependent —> consider adrenal adenoma.
Gold standard: dexamethasone suppression test (overnight - Giving synthetic cortisol to see if the negative feedback kicks in to suppress the cortisol (non-Cushing’s <50 nmol/L)
In Cushing, there is no suppression of cortisol.
Treatment for Cushing’s
Cushing disease:
Trans-sphenoidal resection /
bilateral adrenalectomy (complication of this = Nelson’s syndrome - pituitary continues to enlarge with excess ACTH secretion + hyperpigmentation, no -ve feedback from the adrenal gland)
Otherwise, treat the cause…
Adrenal adenoma:
Unilateral adrenalectomy
Ectopic ACTH = surgical removal of SCLC
Complications of Cushing’s
Osteoporosis
Secondary diabetes mellitus
Depression
Define acromegaly
Clinical manifestation of excessive growth hormone
How does high GH manifest in adults and children
Acromegaly in adults - after epiphyseal fusion
Gigantism in children - before epiphyseal fusion
Cause of acromegaly
Functional pituitary adenoma
Pathophysiology for acromegaly
GHRH —> GH (from somatotrophs) —> IGF-1 (liver) which exerts effects on the rest of the body
In acromegaly… IGF-1 is abnormally high
Signs and symptoms of acromegaly
Large hands and feet
Prognathism
Frontal bossing
Macroglossia
Vision change (bitemporal hemianopia)
Large interdental spaces
Carpel tunnel syndrome
Arthralgia / back pain
Investigations / diagnosis for acromegaly
1st line screening: IGF-1 serum level high
Gold standard: OGTT
Treatment for acromegaly
1st line: always trans-sphenoidal surgery
Or medication…
Dopamine agonist… Bromocriptine
Somatostatin analogue… ocreotide
GH antagonist… pegvisomant
Complications of acromegaly
T2DM
Sleep apnoea
What is the growth hormone inhibiting hormone
Somatostatin
Note: more potent at inhibition than dopamine
Very high glucose can also inhibit it
Define Conn’s syndrome
Primary hyperaldosteronism
I.e. excess aldosterone, independent of the RAAS
Most common cause of secondary hypertension
Difference between primary and secondary hyperaldosteronism
Primary is excess aldosterone independent of RAAS -
for example…
adrenal adenoma (conns syndrome) - 2/3
Or
Bilateral adrenal hyperplasia - accounts for 1/3 of cases
Secondary is excess aldosterone release because of RAAS activation (due to excess renin) -
For example…
renal artery stenosis
Renal artery obstruction
Heart failure
Where is renin secreted from
Juxtaglomerular cell in kidney
How does aldosterone affect the kidneys
Increase sodium reabsorption from the distal tubule
Increase potassium secretion from the distal tubule
Increase hydrogen secretion from the collecting ducts
Pathophysiology for Conns
Adrenal adenoma causes excess release of aldosterone which raises blood pressure… -ve feedback so renin is suppressed.
In secondary hyperaldosteronism, renin is raised.
End up with hypertension with hypokalaemia
Signs and symptoms of hyperaldosteronism
Resistant hypertension (unfixable with ACEi / B blockers)
Hypokalaemia
Muscle weakness
Parasthesia
Polydipsia + polyuria
1st line investigation for conns syndrome / hyperaldosteronism
Renin:angiotensin
Investigations / diagnosis for conns syndrome
1st line: Renin : Aldosterone ratio
Diagnostic: high aldosterone NOT suppressed with 0.9% IV saline or Fludrocortisone
ECG: for hypokalaemia will see… (long PR, U waves and ST depression)
Treatment for conns syndrome / hyperaldosteronism
Surgery - laparoscopic adrenelectomy
SPIRONOLACTONE (aldosterone antagonist) - should be use 4 weeks pre-op
And for bilateral adrenal hyperplasia
What can renal artery stenosis be confirmed by
Renal Doppler ultrasound scan
CT angiogram
MRA
To diagnose DKA you require…
Treatment for DKA
FLUIDS - 0.9% iv saline (sodium chloride)
I
G
P
I
C
K
Risk factor for acromegaly
MEN 1
Define adrenal insufficiency
Reduce secretion of adrenal cortex hormones
Particularly cortisol and aldosterone
Name primary adrenal insufficiency
Addison’s disease
Different types of adrenal insufficiency and why… their pathophysiology
Primary (Addison’s): damage to the adrenal cortex results in reduced hormone secretion… feedback means theres still high ACTH —> only adrenal insufficiency leading to hyperpigmentation
Secondary: reduced ACTH causing a reduced stimulation of adrenal gland, reduced hormone secretion and reduced ACTH
Tertiary: reduced secretion of CRH form hypothalamus so HPA axis suppression —> reduced hormone secretion.
Who’s Addisons more commonly seen in
F > M with other autoimmune condition
Causes for adrenal insufficiency
Primary / addisons:
In developed world =autoantibody mediated adrenal destruction
In developing world = TB (+ sarcoidosis)
Other causes = adrenal metastases (lung, liver, breasts) / Adrenal haemorrhage (e.g. Waterhouse friderichson syndrome—>blood.V in adrenals burst and cause damage to cortex - main cause of this is meningococcal meningitis)
Secondary:
Main cause = iatrogenic ( suppression of HPA axis) - exogenous steroids
Signs / symptoms of adrenal insufficiency
Weight loss
Postural Hypotension (reduced aldosterone)
Vitiligo + reduced body hair (reduced androgens)
Hypoglycaemia (reduced cortisol)
Hyperpigmentation (only in Addison’s)
Investigation / diagnosis of adrenal insufficiency
Short synacthen test:
Tests adrenal reserves by…
Measuring basal cortisol level at 9am (highest here - if low then abnormal)
Give synacthen and sample cortisol 30 mins after and 60 mins after… if failure to double from baseline = primary adrenal insufficiency (should be >580nmol/L)
Other tests:
U&Es… Hyperkalaemia, hyponatraemia
CT / MRI adrenals
Autoantibodies associated with adrenal insufficiency
21-hydroxylase antibodies
Adrenal cortex antibodies
Present in 80% of autoimmune adrenal insufficiency
Treatment for adrenal insufficiency
Hydrocortisone
Fludrocortisone
In trauma / infection —> double the dose of hydrocortisone (cortisol needed in stress)
What is the severe acute presentation of adrenal insufficiency
Adrenal crisis - addisonian crisis
When you have severe adrenal insufficiency ESP hypocortisolemia;
Nausea + vomiting
Renal failure
Loss of consciousness
Presentation of adrenal crisis
Nausea + vomiting
Renal failure
Loss of consciousness
Treatment for adrenal crisis
Immediate IV hydrocortisone
IV saline (0.9% sodium chloride) + dextrose (if hypoglycaemic)
Define diabetes insipidus
3L + of dilute urine daily; due to decreased secretion or action of ADH
Types of diabetes insipidus
Cranial - decreased ADH secretion
Nephrogenic - decreased kidney response to ADH
Other types include: Gestational / Dipsogenic
Cause on central/neurogenic diabetes insipidus
ADH gene mutation
Pituitary adenomas / brain tumours
Idiopathic
Cause of nephrogenic diabetes insipidus
Drugs; Lithium
Renal tubular acidosis
ADH-R mutation
Polyuria
Pathophysiology for diabetes insipidus
Nephrogenic diabetes insipidus is when the collecting ducts of the kidneys do not respond to ADH
Cranial diabetes insipidus is when the hypothalamus does not produce ADH for the pituitary gland to secrete.
Signs / symptoms for diabetes insipidus
Polyuria
Polydipsia
HYPERNATRAEMIA
Severe Dehydration
Confusion
Investigation / diagnosis for diabetes insipidus
Osmolality test:
Urine osmolality = low
Serum osmolality = high
Water deprivation test (no fluid for 8hrs):
Measure urine osmolality and administer desmopressin.
8hrs later, check urine osmolality again.
What is water deprivation test used for and what its result
Diabetes insipidus
Measuring URINE osmolality before and after desmopressin administration
Diagnosis. After deprivation. After desmopressin
Cranial DI. Low. (<300) High (>800)
Nephrogenic DI. Low. Low
Treatment for diabetes insipidus
Cranial - give desmopressin
Nephrogenic - thiazides diuretics + treat underlying cause
Why are thiazides used for nephrogenic diabetes insipidus
Increase water loss at distal convoluted tubule… this encourages increased sodium uptake (+ water retention) which then concentrates the urine and helps with retention of water.
Define SIADH - syndrome of inappropriate ADH
Inappropriate release of ADH - leads to more water retention therefore compensatory sodium excretion to main euvolemia
(Dilute euvolemia)
The excessive water reabsorption is not usually significant enough to cause a fluid overload, therefore you end up with a “euvolaemic hyponatraemia”.
It is OVERDIAGNOSED CAUSE OF HYPONATRAEMIA…
What are the causes of SIADH
Tumours (SCLC, prostate, pancreatic)
Trauma to the head
Infection (TB, pneumonia)
Drugs - thiazides, carbamazepine (schizophrenia), SSRIs
Pathophysiology for SIADH
Increased ADH release independent of RAAS —> increased vessel vasoconstriction and…
Increased Aquaporin-II expression of collecting duct therefore, increased blood volume by water retention
Excess H2O retained means more dilute blood & more Na+ loss to try compensate —> hyponatraemia
Signs and symptoms of hyponatremia
Sx in hyponatremia!!
- Vomiting
- Decreased GCS
- Headaches
- Muscle weakness
Seizures, neurological complications, brain stem herniation
In what condition could a Px get brain stem herniation and what is it
SIADH
Brain stem herniation = low sodium mean increased compensatory H2O movement into brain stem and this increases ICP
Causes hyponatremic encephalopathy
Risk of brain stem herniation through foreman magnum (tectorial herniation)
Investigation and diagnosis of SIADH
U&Es: HYPONATREMIA and normal K+
High urine osmolality - because serum is diluted… urine is concentrated
Definitive diagnosis: to differentiate between Na+ (salt) depletion & SIADH; give 0.9% saline —>
Na+ depletion —> serum osmolality will be correct
SIADH —> serum osmolality fails to correct
Treatment for SIADH
Fluid restriction + hypertonic saline
Treat underlying cause
-tumour excision
Chronic cases —>
Drugs; Tolvaptan (vasopressin antagonist / ADH receptor blocker),
Furosemide,
Demeclocycline (tetracycline antibiotic)
Complication of SIADH
Central pontine myelinolysis
- usually due to rapid correction of sodium
2 phases fro CPM:
Phase 1: encephalopathy and confusion - blood sodium levels fall so water moves via osmosis across blood:brain barrier.
Phase 2: spastic quadriparesis, cognitive and behavioural changes - when given Na+ too fast, get demyelination of neurones.
What cells produce PTH
Chief cells
What triggers PTH
Hypocalcaemia
Role of PTH
Increase osteoclast activity - increases bone resorption
Increases calcium absorption in kidney
Increases calcium absorption in gut
Increases Vit D activity by converting into its active form - Vitamin D acts to increase calcium absorption from the intestine.
What are PTH disorders related to
Related to disorders of Ca2+ metabolism
Hyper PTH = high Ca2+ (cause of 90% of all Hypercalcaemia) - most common cause in community = hyperparathyroidism
Most common in hospital = bone malignancies e.g. myeloma
Hypo PTH = low Ca2+ (main cause is CKD)
Causes of hyperparathyroidism
Primary (most common) - parathyroid adenoma
Sometimes parathyroid adenoma
[hyperparathyroid —> hypercalcaemia]
Secondary - response to low calcium (Vit d deficiency / CKD)
Get compensatory hypertrophy of the parathyroid gland
Chronic lack of calcitriol - this is an agonist for PTH
[hypocalcaemia —> hyperparathyroid]
Tertiary - after many years of secondary hyperparathyroidism (most common = CKD) —> glands act autonomously + release PTH with no -ve feedback (increased PTH regardless of Ca2+ conc)
Malignant: neoplasms (squamous cell lung cancer, breast, renal) secrete PTHrP; this ectopically mimics PTH
Signs and symptoms for hyperparathyroidism
Signs of hypercalcaemia:
Renal stones (calcium oxalate)
Painful bones (excess resorption - osteopenia)
Abdominal groan (constipation, nausea, vomiting)
Psychiatric moans (depression, anxiety)
Investigation and diagnosis for hyperparathyroidism
See haroons table….
PTH - high in all types
Ca+ - high in primary, tertiary…. Low in secondary
Phosphate - low in primary…. High in secondary & tertiary
ALP - high in all types
Treatment for hyperparathyroidism
For primary - removal of parathyroid gland / parathyrodectomy of all 4 glands
For secondary / tertiary - treat cause
complications for hyperparathyroidism
Acute severe Hypercalcaemia;
IV fluids + bisphosphonates
Define Hypoparathyroidism
Reduced PTH hormone secretion
Rarer than hyperparathyroidism
Types of Hypoparathyroidism and their causes
Primary - parathyroid gland failure (diGeorge syndrome —> familial, where parathyroid glands do not develop /// could be idiopathic)
Secondary - after surgery / parathyroidectomy (most common)
Pseudohypoparathyroid -
when theres peripheral PTH resistance
- Have small stature + small 4th/5th metacarpals
Signs / symptoms of Hypoparathyroidism
Signs / symptoms of Hypocalcaemia
Symptoms: Remember Numb CAT
- Convulsions, Arrhythmias, Tetany and Numbness
Signs:
Chvostek - twitching of facial muscles (when CN7 traps over parotid)
Trousseau - carpopedal spasm (when tourniquet applied to forearm)
Investigation / diagnosis for Hypoparathyroidism
TFTs + U&Es :
Low PTH
Low Ca2+
High Phosphate
ECG :
Long QT
Treatment for Hypoparathyroidism
Remember its low Ca2+
Give calcium supplies + Vit D (AdCal D3)
What can cause Hypercalcaemia
Hyperparathyroidism
Bone malignancy
^^ most common ^^
Drugs - thiazides
Excess calcium intake
Dehydration
Hyperthyroidism
What’s seen on ECG finding for Hypercalcaemia
Short QT interval
Signs / symptoms for Hypercalcaemia
Renal stones
Painful bones
Psychiatric moans
Abdominal groans
Decreased muscle tone + contractions because calcium inhibits fast Na+ influx
What will PTH look like in Hypercalcaemia
PTH will be low;
-ve feedback
Unless in hyperparathyroidism
Causes of hypocalcaemia
CKD (decreased activation of Vit D)
Severe Vit D deficiency
Hypoparathyroidism
Drugs; bisphosphonates / calcitonin
Acute pancreatitis
ECG finding for hypocalcaemia
Long QT interval
Signs / symptoms for hypocalcaemia
Numb CAT
- Numbness, Convulsions , Arrhythmias, Tetany
Increased muscle tone + contractions
What happens to PTH in hypocalcaemic state
PTH is high
Unless in Hypoparathyroidism
Define Hyperkalaemia
> 5.5mmol/L
6.5 mmol/L = emergency
Causes for Hyperkalaemia
AKI
Drugs; Spironolatone, ACEi
Addison’s
DM ( + DKA)
Pathophysiology of Hyperkalaemia
Increased K+ decreases threshold for Action Potentials - easier depolarisation for tissue
+ abnormal heart rhythms
Signs / symptoms of Hyperkalaemia
Fast irregular pulse (increased risk of V.Failure)
Myalgia
Investigations / diagnosis for Hyperkalaemia
U&Es
High K+ levels
ECG (remember as…
GO Absent p waves
GO LONG Prolonged PR
GO TALL Tall tented T waves
GO UNDER Wide QRS complex
Treatment for Hyperkalaemia
Urgent (to stabilise cardiac membrane):
1st line: Calcium gluconate
Then: insulin + dextrose (glucose)
Non-urgent (to treat just Hyperkalaemia; no cardiac issues):
Insulin + dextrose
Define hypokalaemia
< 3.5 mmol/L
<2.5 mmol/L = emergency
Causes of hypokalaemia
Drugs; thiazides (Na+ sparing, K+ excreting) / loop diuretics
Conn’s (hyperaldosteronism)
Renal Tubular Acidosis 1 + 2
Decreased potassium intake
Signs / symptoms of hypokalaemia
Hypotonia
Hyporeflexia
Arrhythmias (esp. AFib)
Investigation / diagnosis of hypokalaemia
U&Es : decreased K+
ECG :
small inverted T waves
Prominent U waves
ST depression
PR prolongation
Treatment for hypokalaemia
K+ replacement
Aldosterone antagonist / K+ sparing diuretic = spironolactone
Define carcinoid tumours / syndrome
Poorly malignant tumours of enterochromaffin cells (neuroendocrine cells - can be found all over body; particularly GI organs)
Where is carcinoid tumours mostly found
GI tract - at appendix + terminal ileum
Can also be found in lungs
Syndrome - when tumour metastasises in liver; causing Sx
Difference between carcinoid tumour and syndrome
C. Tumours = only referring to the neoplastic cells (little to no symptoms)
C. Syndrome = when tumour metastasises to the liver —> Sx
Pathophysiology of carcinoid tumour / symptoms
Neuroendocrine cells found particularly in GI tract / lungs
These cells get signals from nerve cells to secrete hormones into blood…
Amines (histamine) / (serotonin)
Polypeptides (bradykinin) - a vasodilator
Prostaglandins - potent vasodilators
These can be regulated by other hormones e.g. somatostatin inhibits serotonin.
Normally: Serotonin enter liver —> some metabolised into 5-hydroxyindolacetic acid (5-HIAA) & excreted via urine…
The rest carried in blood giving various effects.
When theres a N.E tumour, uncontrolled + unregulated N.E cell division (mainly in GI) —> if met. To liver = carcinoid syndrome.
Liver can’t metabolise hormone so build up of above hormones (their increased action) —> Sx!!!
Effects or role of serotonin
In GI tract:
Increased motility & peristalsis
In vasculature:
Platelets take up serotonin and later use to vasoconstrict
In heart connective tissue:
Stimulates fibroblasts (get increased collagen)
Primary site for N.E. Tumours
Common: Small/large intestine, lung, liver
Then: stomach, pancreas, ovaries, thymus
Secondary sites for neuroendocrine tumour/carcinoid tumour
Liver
This can be primary / secondary… but causes carcinoid syndrome
What symptoms are experienced in carcinoid syndrome
Common Sx :
Flushing + itching, SoB, diarrhoea
Why..?
- Flushing + itching —> increased histamines & bradykinin
- Right sided heart valve incompetence (tricuspid regurgitation / pulmonary stenosis) - fibrosis
- SoB - bronchoconstriction because of fibrosis
- Diarrhoea and renal impairment - fibrosis of abdominal mesenteries + impaired kidney function - fibrosis
^^ all because of increased serotonin^^
Also, increased serotonin decreases tryptophan —> decreases niacin —> get pellagra (Sx: dermatitis, confusion)
What exaggerates / heighten carcinoid syndrome Sx
Alcohol
Emotional stress
Investigation / diagnosis of carcinoid tumours / syndrome
Liver USS —> +ve metastisis
Urinalysis —> increased 5-HIAA (serotonin metabolite) in urine ///chromagranin-A is also elevated + coupled with OCTREOSCAN (GoldStandard)
CT/MRI to locate primary tumour
Treatment of carcinoid tumour / syndrome
Surgical excision - definitive
Octreotide (SST ANALOGUE) —> bind to N.E. Cells to block production of hormones
Complications of carcinoid tumour / syndrome
Carcinoid crisis - life threatening Sx constellation
Treatment - high dose somatostatin analogue
Define Prolactinoma
Prolactin = endocrine hormone secreted by anterior pituitary
…..…oma = refers to tumour
So, Prolactinoma is benign tumour (adenoma) of the pituitary gland which secretes excess prolactin
Where is prolactin secreted from
Lactrotrophs found in anterior pituitary
Where does LH + FSH come from and what’s their role
Gonadotrophs in anterior pituitary
Role:
Stimulate ovaries in women —> for oestrogen
Stimulates testes in men —> for testosterone
What hormones are secreted by hypothalamus to control prolactin release
Thyrotropic-releasing hormone —> stimulatory … but …
Dopamine —> inhibitory … and …
overrides TRH for prolactin release so in non-pregnant women there’s a constant release of dopamine to control limited release of prolactin
Pathophysiology for prolactin
High levels of prolactin should send a -ve feedback to hypothalamus to increase dopamine levels… to then lower prolactin
High levels of prolactin should send a -ve feedback to hypothalamus to decrease GnRH… lowering FSH + LH —> less oestrogen / testosterone production —> decreased ovulation / spermatogenesis
Remember: oestrogen in women also PREVENTS osteoclast activation —> decreased bone breakdown … BUT … when oestrogen reduced you get too much resorption —> fractures and osteopenia
In a tumour… excess release of this hormone regardless of -ve feedback
< 10mm —> micro Prolactinoma
> 10mm —> macro Prolactinoma —> these can press on surrounding structures:
Meninges (pain at brain)
Optic chiasm (bitemporal hemianopia) - tunnel vision
Cause of prolactinemia
Pituitary adenoma
Drugs; ecstasy
How is breast milk produced
A. Pituitary secretes prolactin +
From placenta, human placental lactogen + progesterone are secreted
All 3 stimulate breast glandular tissue to make milk
Hyperprolactinaemia effects on oestrogen
High levels of prolactin should send a -ve feedback to hypothalamus to decrease GnRH… lowering FSH + LH —> less oestrogen / testosterone production —> decreased ovulation / spermatogenesis
Remember: oestrogen in women also PREVENTS osteoclast activation —> decreased bone breakdown … BUT … when oestrogen reduced you get too much resorption —> fractures and osteopenia
Signs / symptoms of Prolactinoma
Micro Prolactinomas are usually asymptomatic
Macroprolactinomas:
bitemporal hemianopia
Headaches
Galactorrhoea
Amenorrhoea (F)
Gynecomastia (M)
Erectile dysfunction (M)
Decreased libido & infertility
Investigation / diagnosis of Prolactinoma
Blood test: Increased prolactin
Treatment for Prolactinoma
Best: Dopamine agonist (Bromocriptine, Cabergoline) - massively shrinks tumour
Surgery
Define pheochromocytoma
Phoenix… = dark
Chromo = colour
Cyt = cell
oma. = tumor
So, Phoechromocytoma is a adrenal medullary tumor where cells (chromaffin cells) darken when tumour is formed.
Pathophysiology of pheochromocytoma
Adrenal medulla; chromaffin cells secrete catecholamines (Ad / NaD) - trigger fight / flight
These hormones bind to al[ha / beta recpetors to…
Increase cardiac output
Increased blood pressure
Dilate pupils
Increase blood sugar
Mutation / spontaneous uncontrollable division of these cells increase secretion
Increased catecholamines —> Cause smooth muscle contraction —> vasoconstriction —> increases peripheral vascular resistance —> hypertension
Where in the body can chromaffin cells be found
Adrenal medullar
Carotid arteries
Bladder
Abdominal aorta
Cause of pheochromocytoma
Sporadic
Or
Inherited:
MEN 2a / 2b (multiple endocrine neoplasia)
Neurofibromatosis type 1 (tumour deposits along nerve myelin sheaths)
What can trigger catecholamine release
Stress
Physical exertion
Foods containing tyramine (chocolate, cheese, wine)
Complication of pheochromocytoma
Hypertensive crisis / emergency:
180/120mmHg
Small vessels break:
Heart - CHF
Brain - Ischaemic / haemorrhagic stroke
Eyes - Retinol haemorrhage
Kidney - Kidney failure
Treatment for hypertensive crisis
Phentolamine - alpha blocker
Signs / symptoms of pheochromocytoma
Hypertension - cause of secondary hypertension (rarer than Conn’s)
Palpitations
Sweating
Pallor
Tachycardic
Investigations / diagnosis for pheochromocytoma
Plasma metanephrine / normetanephrine (diagnostic)
These are more sensitive readings and longer half life
Also:
Urinalysis - catecholamines
CT; image of tumour
Treatment of pheochromocytoma
Drugs;
Alpha-blockers (phenoxybenzamine)
Then
Beta-blockers (Atenolol)
^^prevents reactive vasoconstriction^^
Surgery; to remove tumour
Tx for hypoglycaemia ()
If alert; sugary drinks, gels and snack
Unconscious + out of hospital; intramuscular glucagon
Unconscious + in hospital; intravenous dextrose
Give 4 medications you can give for diabetic neuropathic pain
Amytryptiline
Gabapentin
Pregabalin
Duloxetine
Which receptors are commonly seen in graves
Anti-TSH receptor antibodies
