Endo - general Flashcards
Drugs that can cause DI
- Lithium
- Gentamicin
- Rifampin
- Colchicine
- Cisplatin
- Demeclocycline
- Orlistat
Drugs that can cause T2DM
- Thiazide diuretics
- Corticosteroids
- Atypical anti-psychotics
- Antiretroviral protease inhibitors
Complications of DKA
- Cerebral oedema (mannitol infusion, mechanical ventilation)
- Pulmonary oedema
- ARDS
treatment related reduction in colloid volume –> water accumulation in the lungs –> decreased lung compliance + hypoxaemia
monitor blood O2 levels, lower fluid intake, replace colloid - Iatrogenic hypoglycaemia
- Iatrogenic hypokalaemia
- Arterial/venous thromboembolism
- prophylatic heparin
- gastric stasis
Plasma osmolarity equation
2 (Na+K) + glucose + urea
Anion gap equation
Generally used formula, K is excluded on the grounds that its value is small enough to be disregarded
Na - (Cl + HCO3)
Formula used when the value of the K is expected to vary significantly as in renal patients (+ is the one that is on bb)
(Na + K) - (Cl+ HCO3)
Describe the plasma osmolarity in DKA + HONK
Increased in both DKA + HONK (both are hyperosmolar states)
Much higher in HHS/HONK
o >290 mOsm/kg + ketonaemia/ketonuria - DKA
o >320 mOsm/kg + no significant ketonaemia/ketonuria - HHS/HONK
Actions of insulin
- Glucose uptake
- Increase in glycogen synthesis
- Decreased gluconeogenesis and glycogenolysis
- Increase fat synthesis
- Decreased lipolysis
- Increased amino acid uptake
- Decreased proteolysis
- Increased potassium uptake
- Increased phosphate uptake
- Decreased renal sodium excretion
Factors that
- Increase Ca
- Derease Ca
and where are they produced
Increase
- Calcitriol (skin + UV light)
- PTH (parathyroid glands)
Decrease
- Calcitonin (parafollicular cells of thyroid gland)
How does vitamin D get converted to active Vitamin D (calcitriol)?
Diet + UV light form vitamin D (skin)
25 hydroxylase turns vitamin D to 25-hydroxyvitaminD3 (liver)
1a-hydroxylase turns 25-hydroxyvitamin D3 into 1,25-dihydroxyvitaminD3 (calcitriol, activated vitamin D) (kidney)
PTH increases renal production of 1,25-dihydroxyvitaminD3
Function of PTH on kidneys, bone, small intestines
+ resultant effect
Kidneys
1a hydroxylase stimulation
Increase calcium absorption
Increase phosphate excretion
Bone
Increased bone resorption
Intestines
Increased calcium absorption
Increased phosphate absorption
Resultant effect
- Increased Calcium
- Decreased phosphate
Calcitriol raises blood calcium levels more than PTH
Function of calcitriol/Vitamin D on kidneys, bone, small intestines
+ resultant effect
Kidneys
Increase calcium absorption
Decreased phosphate reabsorption
Bone
Increased bone resorption
Intestines
Increased calcium absorption
Increased phosphate absorption
Resultant effect
- Increased Calcium
- Decreased phosphate
Calcitriol raises blood calcium levels more than PTH
Which 2 substances provide negative feedback to the parathyroid gland?
High Calcium
High Calcitriol
Which substance should be used to monitor vitamin D levels?
25-hydroxyvitamin D
- Major circulating form of vitamin D used to determine vitamin D status
NOT 1,25-dihydroxycholecalciferol
Causes of secondary hyperPTH
- Vitamin D deficiency Poor sunlight Poor dietary intake Malabsorption - CKD - Liver disease
Endo causes of proximal myopathy
- Cushing’s
- Osteomalacia (2ndary hyperparathyroidism)
- Thyrotoxicosis (hyperthyroidism enhances metabolism of 25-hydroxyvitamin D)
What is MEN 1?
Pituitary tumours
Pancreatic tumours
Parathyroid gland hyperplasia
What is MEN2A?
Medullary thyroid cancer
Phaechromocytoms
Parathyroid gland hyperplasia
What is paget’s disease?
- Disease of bone remodelling
- Excessive bone resorption followed by excessive bone growth
- Results in abnormal “mosaic pattern” of lamellar bone (new bone that is being build is woven and not lamellar)
- The marrow spaces are filled by an excess of fibrous tissue with a marked increase in blood vessels
- This leads to skeletal deformities and potential fractures
- Most often it involves the skull, lumbar vertebrae, pelvis, femur
Which are the three main phases of Paget’s disease?
- Lytic phase - osteoclasts - demineralisation + bone resorption
- Mixed phase - lytic phase + blastic phase (rapid disorganized proliferation of new bone tissue by osteoblasts)
- Sclerotic phase - bone formation exceeds bone resorption - structurally disorganised bone (weaker than normal healthy bone, woven bone not lamellar)
- Burned out state - osteoblastic activity slows down + there is a dormant state in the disease
Definition of osteoporosis
reduced bone density resulting in bone fragility and increased fractured risk
T-score < -2.5
What is the difference between the T score and the Z score in a DEXA scan?
What does a T-score of < -2.5 mean?
o T score = the number of S.D. the bone mineral density measurement is above or below the YOUNG NORMAL mean bone mineral density
Used to define osteoporosis
o Z score = the number of S.D. the measurement is above or below the AGE-MATCHED mean bone mineral density.
Used to identify patients who may need a work-up for secondary causes of osteoporosis
T-score of < -2.5 = means 2.5 SD or more below the young adult reference mean i.e. less than -2.5 SD therefore -3.5, -4.5 etc
List some RF for osteoporosis
Primary - post menopausal, old age >50 years
Secondary
Drugs - steroids, thyroxin
Endo - Cushing’s, primary hyperparathyroidism, hyperthyroidism, hypogonadism
Cancer - myeloma, metastatic carcinoma
MSK - RA, ankylosing spondylitis, SLE
GI - coeliac disease, IBD
- Post-menopause
- Primary hypogonadism/Secondary amenorrhea – low oestrogen can lead to decreased bone mineral density
- Late menarche/early menopause
- Corticosteroid use (antagonise vitamin D and therefore decrease calcium absorption from the gut)
- Glucocorticoid excess e.g. Cushing’s syndrome
- Vitamin D deficiency
- Low calcium intake
- Prolonged immobilisation/Physical inactivity
- Low BMI
- Smoking, Alcohol
- FHx
- F>M
- > 50 women
- > 65 men
- Afro-carribeans have a higher bone mass than Caucasians
Function of excess PTH
- Stimulates osteoclasts to break down bone
* Makes kidneys hold on to calcium + get rid of phosphate - hypercalcemia, hypophosphatemia
What causes primary hyperparathyroidism?
Parathyroid adenoma
Parathyroid hyperplasia
Parathyroid carcinoma
Parathyroid gland makes PTH independently of the calcium level
RF – MEN1, MEN2A, HTN
What causes tertiary hyperparathyroidism?
- Individuals who have had secondary hyperparathyroidism for many years develop primary hyperparathyroidism
- Chronic stimulation of the parathyroid gland by low Ca results in autonomous PTH secretion even after the cause of hypocalcaemia has been corrected
- Makes PTH independently of calcium levels –> hypercalcaemia
Causes of vitamin D deficiency
• Poor sunlight
• Poor dietary intake
• Malabsorption
• Old age
o Decreased ability of skin to produce vitamin D
• Obesity – body fat stores vitamin D
• CKD
• Granulomatous diseases (e.g. sarcoidosis, TB) – enhanced destruction of Vitamin D
• Hyperthyroidism – enhances metabolism of 25-hydroxyvitamin D
• Medication use – glucocorticoids, antiepileptic medication, rifampicin, St John’s wort
vitamin D deficiency = secondary hyperparathyroidism = osteomalacia
Definition of DI
Inadequate secretion or insensitivity of the renal collecting ducts to ADH leading to hypotonic polyuria
(Craniopharangyomas are much more likely to cause cranial DI than actual pituitary tumours e.g. prolactinomas)
Type of acid-base derangement in Cushing’s syndrome
hypokalaemic metabolic alkalosis
Definition of DKA
Glucagon driven breakdown of fatty acids to ketones
In the setting of insulin deficiency, stress hormones like glucagon, cortisol, catecholamines increase glucose and stimulate ketogenesis
Na status in patients with DKA
Pseudohyponatraemia due to increased glucose in the blood
Distiniguished from true hyponatraemia in the following way
Pseudohyponatraemia - N/High plasma osmolarity
High –> hyperglycaemia
N –> hyperlipidaemia, hyperproteinaemia
True hyponatraemia - Low plasma osmolarity
What is myxoedema maddness?
Psychosis with delusions and hallucinations or dementia
Occurs in severe hypothyroidism
May be seen in the elderly after starting levothyroxine treatment
What is Plummer’s disease?
One type of hyperthyroidism
Toxic multinodular goitre on producing TSH on one side of the thyroid gland
This causes the other side to atrophy
Give some examples of conditions that cause thyrotoxicosis without hyperthyroidism
Technetium scan uptake
Mx
Autoimmune thyroiditis
Postpartum thyroiditis
Subacute/de Quervains thyroiditis
Amiodarone-indiced thyroiditis
Low uptake
Mx
- B blockers
- Thinoamides (propylthiouracil, carbimazole) wont work - problem is not that thyroid is overactive but that it has been damaged + released the hormones prematurely
Pathophysiology of Grave’s disease
Antibodies/Plasma IgG to thyroid TSH receptor stimulates thyroid hyperplasia and thyroid hormone hypersecretion, causing exaggerated thyroid hormone action and autonomic overactivity.
Type V hypersensitivity
List the 5 types of thyroid cancer
Which is the most common
Which has the worst prognosis
Papillary thyroid carcinoma 30-50 y/o
Follicular thyroid carcinoma 40-60 y/o (particulalry metastasises to the lungs)
Medullary thyroid carcinoma
Primary thyroid lymphoma (almost always non-Hogkin;d lymphoma)
Anaplastic carcinoma 60-70 y/o
Papillary thyroid carcinoma - most common
Anaplastic carcinoma - worst prognosis (mean survival is 6m)
Hashimotos thyroiditis
What is it Epidemiology Presentation Biopsy Associated with
What is it - chronic autoimmune thyroiditis, causes hypothyroidism
T-lymphocyte infiltration of the gland + reactive ab against TSH receptor + less commonly TG
T cell mediated destruction of the thyroid gland
Type IV hypersensitivity
Epidemiology - middle age and elderly
Presentation - symptoms of hypothyroidism, firm non-tender goitre
Moves on swallowing
Biopsy
Lymphocytic infiltrate
Destruction of follicles
Variable fibrosis
Associated with - personal/FHx of other autoimmune conditions
Commonest cause of goitre in developed countries
Commonest cause of goitre worldwide
+ other causes
developed countries – Graves (hyperthyroidism)
worldwide – iodine deficiency (hypothyroidism)
other causes
iatrogenic - post surgery, radioiodine, amiodarone
congenital dysgenesis
de Quervain’s thyroditis
Causes of nephrogenic DI
- Hypercalcaemia
- Hypokalaemia
- Lithium
- Inherited (AVPV2 gene)
- Idiopathic
MEN
Inheritance pattern
Defect on which genes + on which chromosomes for MEN1, MEN2A, MEN2B?
AD
MEN1
MEN1 gene on Chr 11
Tumour suppressor gene
MEN 2A, MEN 2B
RET gene on Chr 10
Proto-onco gene
What do carcinoid tumours release?
Humoural factors
o Amines (SEROTONIN, histamine) o Polypeptides (bradykinin - vasodilator) o Prostaglandins (vasodilators)
Where are carcinoid tumours commonly found?
Anus + rectum
Why in carcinoid syndrome are there no symptoms unless the tumours metastasise to the liver?
Because hormones released in the portal circulation are metabolised in the liver, therefore liver dysfunction decreases the liver’s ability to metabolize the hormones which get released from neuroendocrine cells allowing them to build up and cause symptoms
Hepatic metastases result in the secretion of tumour products into the hepatic vein
This is the most common site for a neuroendocrine tumour to metastasize
Carcinoid syndrome RF
• Genetic MEN1 syndrome (neuroendocrine tumours are associated with MEN-1)
Adrenal histology and what hormones are being produced where
Adrenal cortex
Zona glomerulosa - mineralocorticoids e.g. aldosterone
Zona fasciculata - glucocorticoids e.g. glucose
Zona reticularis - sex steroids
Adrenal medulla - catecholamines
Definition and causes of primary hyperalodteronism
Autonomous aldosterone overproduction from the adrenal gland with subsequent suppression of plasma renin activity
Conn’s syndrome/ adrenal adenonma (70%) - young females
Bilateral adrenal cortex hyperplasia (30%)- old males
Familial hyperaldosteronism
aldosterone producing adrenal carcinoma
DDx for a presentation of HTN + Hypokalaemia
- Conn’s syndrome/bilateral adrenal hyperplasia - high aldosterone, low renin
- RAS - all pt will have HTN + hypokalaemia
- Cushing’s disease may also present with HTN + hypokalaemia - low aldosterone, low renin
Causes of Cushing’s syndrome
Exogenous causes
• Exogenous cortisone (e.g. prednisolone) – MOST COMMON CAUSE
Endogenous causes
• Cushing’s disease –> ACTH secreting pituitary tumours
• Ectopic ACTH secreting tumours (small cell lung cancer, bronchial carcinoids)
• Autonomous adrenal cortisol overproduction (adenomas (benign), carcinomas (malignant), bilateral adrenal hyperplasia)
What is a phaeochromocytoma?
Tumour arising from catecholamine-producing chromaffin cells of the adrenal MEDULLA
10% are extra-adrenal (paragangliomas)
10% are bilateral
10% are malignant
consider phaeos in patients with
Young onset
Resistant intractable HTN
Which familial sydroomes are assosciated with phaeochromocytoma?
- MEN 2A, 2B
- NF1
- Von Hippel-Lindau
Commonest cause of adrenal insufficiency in the UK vs woldwide
UK - autoimmune addison’s
Worldwide - TB addison’s
but generally most common causes are iatrogenic
primary causes are rare
With which syndrome is Addison’s disease related?
AIPES
Autoimmune polyendocrine syndrome
Type 1 - AR caused by mutations in the AIRE gene
Type 1
• Addison’s disease
• Chronic mucocutaneous candidiasis
• Hypoparathyroidism
Type 2 • Addison’s disease • T1DM • Hypothyroidism • Hypogonadism
Pathophysiology of PCOS
- Hyperinsulinemia –> excess insulin binds to theca cells –> causes them to grow and divide -> too many LH receptors
- Increased LH production from anterior pituitary –> stimulates theca cells to produce androgens (androstenedione)
- Granulosa cells overloaded cant convert enough androgen to oestradiol –> build up of androgens in the blood –> symptoms
- Because the LH levels are really high, there’s no LH surge to trigger the dominant follicle to break away from the ovary so it may remain there appearing as a cyst or it might degenerate with the other follicles –> ovulation doesn’t occur
• Insulin resistance –> hyperinsulinemia:
o Increased androgen production
o Decreased production of SHBG in the liver (free testosterone may be raised even if total testosterone is normal)
Top 2 dx if you suspect SIADH
SIADH is not a dx
- Chest XR (lung caner)
- Head CT (brain tumour)
(you don’t really start with brain MRI, CT is usually first line)
Why is prolactin increased in hypothyroidism?
Because excess TRH released to stimulate the pituitary gland to stimulate the thyroid also has a role in stimulating prolactin release
Endocrine tests in multinodular goitre
Normal
BP targets for diabetic
with vascular damage (e.g. diabetic retinopathy)
without vascular damage
with vascular damage (e.g. diabetic retinopathy) - <130/80 mmHg
without vascular damage - <140/90 mmHg
Hyponatraemia + hyperkalaemia unresponsive to IV rehydration dx
Addison’s disease
low serum cortisol, high ACTH
What is Pemberton’s sign?
Elevation of arms above the head –> facial venous congestion + plethora due to thoracic inlet obstruction by retrosternal mass (e.g. goitre)
Type of hypersensitivity
Graves
Hashimotos
Graves - Type V hypersensitivity
Antibody mediated stimulation of the TSH receptor
Hashimotos - Type IV hypersensitivity
T cell mediated destruction of the thyroid gland
T scores in osteoporosis vs ostopenia
Osteoporosis less than minus 2.5 (i.e. -3.5, -4.5)
Osteopenia between minus 1 and minus 2.5
Hypopituitarism, list the order with which the hormones will be affected
LH/FSH
GH
TSH
corticotrophin
Cushin’s disease
which of the following is likely to be decreased/inhibited?
protein catabolism free water clearance circulating neutrophils uric acid production circulating lymphocytes
circulating lymphocytes (suppression of the immune system + t cell responses)
commonest cause of adrenal insufficiency
autoimmune (UK)*
TB (worldwide)
*immune reaction against 21-hydroxylase - destruction of the adrenal cortex
Most common cause of Cushing’s syndrome
Pituitary adenoma that secretes cortisol
How does Cushing’s syndrome / high levels of cortisol / steroids lead to increased risk of infections?
Decrease in circulating lymphocytes
Suppression of the innate immune + T cell responses resulting in lymphopenia
C peptide interpretation
C-peptide indicates ENDOGENOUS insulin production
low in T1DM
high in T2DM
If C-peptide is ABSENT but there are symptoms of hypoglycaemia then it means EXOGENOUS insulin production
T2DM BP monitoring - how often?
>150/90mmHg
>140/80mmHg
>130/80mmHg with renal/ophthalmic/cerebrovascular pathology
T2DM BP monitoring
>150/90mmHg – every month
>140/80mmHg – every 2 months
>130/80mmHg with renal/ophthalmic/cerebrovascular pathology – every 2 months
