ENDO 1 Flashcards
Presentation of DKA:
Abdominal pain
Kussmaul breathing
Polyuria
Polydipsia
Nausea and vomiting
Acetone breath
Dehydration
Hypotension
Altered consciousness
Presentation of HHS:
Elderly patient with T2DM
Over many days, insidious onset
Dehydration, polyuria, polydipsia
Lethargy
Nausea and vomiting
Consciousness altered
Focal neuro deficits
Hyperviscosity
Pathophysiology of T1DM:
Autoimmune destruction of pancreatic islet beta cells that produce insulin.
Absolute insulin deficiency.
Children / early adult life, tend to present in DKA or at least slightly unwell.
Pathophysiology of T2DM:
Defective insulin secretion
Failure of insulin sensitive tissue to respond
Relative insulin deficiency due to excess adipose tissue (not enough to go around the excess fatty tissue, leading to blood glucose increasing).
Thyroiditis vs Grave’s disease?
Thyroiditis - initially hyper then hypo in most cases:
More acute onset
Recent illness
Change in symptoms over weeks (Subacute thyroiditis)
Investigation: thyroid scintigraphy = globally reduced uptake of iodine-131
Graves:
Autoantibodies present e.g. TSH receptor antibodies (TRAb), TPO
Eye signs e.g. exopthalmos, ophthalmoplegia
Pretibial myxedema, thyroid acropachy with clubbing and soft tissue swelling hands and feet and periosteal new bone formation.
Thyroid scintigraphy = INCREASED uptake of radioactive iodine
Causes of raised prolactin (excess stimulation of the anterior pituitary):
Pituitary adenoma
Antipsychotics (dopamine antagonists that inhibit dopamine receptor; usually prolactin is inhibited by dopamine. More common in typical antipsychotics.)
Pregnancy
Oestrogens
Physiological - sleep, stress, exercise
Acromegaly (1/3 of patients)
PCOS
Primary hypothyroidism, due to TRH stimulating prolactin release.
Causes of primary gonadal failure:
Turner syndrome
CAH
Anorexia
ECG changes in hyperkalaemia:
Tented T waves occurs first
Loss of p waves
Broad QRS
Sinusoisal wave pattern
VF
Emergency treatment of hyperkalaemia.
Mild 5-5-5.9
Mod 6-6.5
Severe >=6.5, or ECG changes = emergency treatment:
IV calcium gluconate to stabilised myocardium, Insulin/dextrose infusion causes short term shift from ECF to ICF. +/- nebulised Salbutamol, temporary etc.
Causes and symptoms of hypocalcaemia:
Tetany; muscle twitching, cramping and spasm.
Perioral paraesthesia
Chronic = depression, cataracts
ECG = prolonged QT.
Trousseau’s sign
Chvostek’s sign
Vit D deficiency / osteomalacia
CKD
Hypoparathyroidism
Pseudohypoparathyroidism
Rhabdomyolysis initial stages
Magnesium deficiency (end organ PTH deficiency)
Massive blood transfusion
Acute pancreatitis
Causes and symptoms of hypercalcaemia:
Bones, stones, groans, psychic moans.
Corneal calcification.
Shortened QT on ECG
Hypertension
RENAL failure
Cancer
Hyperparathyroidism
- Primary hyperparathyroidism, most common cause in non-hospitalised patients.
- Malignancy, most common cause in hospital.
Treatment of hypocalcaemia vs hypercalcaemia:
Severe (carpopedal spasm, tetany, seizure, prolonged QT)= IV replacement , IV calcium gluconate 10ml 10% over 10 mins.
Hyper management: rehydration with normal saline, 3-4 litres per day. +/- bisphosphonates following rehydration.
Other options: calcitonin which has quicker effect than bis, steroids in sarcoidosis.
Symptoms associated with Cushing’s syndrome (high levels of glucocorticoid in the body):
Central obesity
Striae
Moon facies
Plethoric complexion
Buffalo hump
Proximal limb muscle wasting
Hirsutism
Easy bruising, poor skin healing
Hyperpigmentation of skin in Cushing disease only (high ACTH levels)
+ Hypertension, cardiac hypertrophy, T2DM, dyslipidaemia, osteoporosis and adverse mental health inc insomnia
Pathophysiology of acromegaly:
Excess growth hormone secondary to pituitary adenoma in over 95% of cases.
Minority caused by ectopic GHRH or GH production by other tumours e.g. pancreatic.
Causes and symptoms of adrenal insufficiency:
Addison’s = autoimmune destruction of adrenal glands, causing reduced cortisol and aldosterone.
Lethargy, weakness, anorexia, n&v, weight loss, salt craving.
Hyperpigmentation - primary Addison’s only
Vitiligo, loss of pubic hair in women, hypotension, hypoglycaemia, hyponatraemia, hyperkalaemia.
Crisis = collapse, shock, pyrexia.
Other causes:
(Primary) = TB, mets, meningococcal septicaemia, HIV, APS
(Secondary) = pituitary disorders
Causes and symptoms of hypopituitarism:
Causes:
Compression, pituitary apoplexy, Sheehan’s syndrome, hypothalamic tumours e.g. cranioph, trauma, radiation, also infiltrative causes e.g. sarcoidosis, haemochromatosis
LOW OF ALL THE HORMONES OF THE PITUITARY:
ACTH (tired, postural hypotension), GnRH (low fsh, lh, amenorrhoea, infertility, libido loss), GH (childhood = short stature), PROLACTIN (lactation problem), TSH (cold, constipation)
Diagnostic criteria for PCOS:
Rotterdam criteria; 2 of 3 present:
US evidence of cysts >=12, 2-9mm in size, uni or bilateral, one of both ovaries increased ovarian vol of >10cm3
Hyperandrogenism = hirsutism, infertility, acne, elevated total or free testosterone
Anovulation /amenorrhoea
Investigations in suspected PCOS and what they might show:
Pelvic US - multiple cysts
?Raised LH:FSH ratio, but not diagnostic
Testosterone normal or mildly elevated
Prolactin normal or mildly elevated
SHBG normal or low
Impaired glucose tolerance
Management of DKA. Is it different in children?
FLUID REPLACEMENT, isotonic saline even if acidotic. 5-8 litres deplete usually.
IV insulin infusion fixed rate. Continue long acting insulin, stop short acting insulin.
Once blood glucose <14, add 10% dextrose to the NaCl 0.9% regime.
Correct electrolytes, e.g. potassium
?Slower infusion in younger adults / children due to greater risk of cerebral oedema.
Management of HHS:
Fluid replacement; estimated losses between 100-220 ml/kg, IV NaCl 0.9%
0.5/1l / hour
Monitor potassium
Don’t give insulin unless blood sugars stop falling with fluids
VTE proph, older population and hyperviscosity
Vascular complciations can occur due to hyperviscosity e.g. MI and stroke.
Investigating thyroid function:
Thyroid examination
TFTs - serum TSH. T3 and T4
Auotantibodies
ESR and CRP
Doppler US
Thyroid scintigraphy and radio-uptake scan
Also ECG if irregular pulse was noted to rule out AF
Thyroid differentials and distinguishing factors (Grave’s, subacute, hashimoto’s, toxic multinodular goitre):
Grave’s disease - goitre, eye disease, autoantibodies esp TRAb, and also TPO. Scintigraphy high / increased uptake.
Subacute / De Quervain’s thyroiditis; preceding viral illness, presents with hyper, painful goitre and raised ESR, then euthyroid for 1-3 weeks, then hypo for a few months. Scintigraphy low uptake.
Hashimoto’s - chronic autoimmune, female, transient thyrotoxicosis at the start. Firm, non-tender goitre, anti TPO and Thyroglobulin antibodies. Associated with MALT lymphoma.
Toxic multinodular goitre - patchy uptake on scintigraphy. Goitre.
Risk factor for gestational diabetes:
Obesity BMI >30
Previous GD in pregnancy
Prev macrosomic baby >4.5kg
First degree relative GD
Family origin; South Asian, black caribbean and middle eastern
Cut off for gestational diabetes, and management:
Fasting >=5.6
2hr post OGTT >=7.8
Fasting <7mmol, trial diet and exercise for 1-2 weeks.
Fasting >7, start insulin straight away, or if between 6.1 and 6.9 and evidence of e.g. macrosomia.
Types of secondary diabetes, and how to they differ from T1DM / T2DM?
Pancreatic diabetes e.g. pancreatitis and pancreatic cancer
Cushing’s syndrome
Acromegaly
Steroids
Investigations in suspected adrenal disease / Cushing syndrome:
Consider iatrogenic, ACTH dep and indep causes.
HYPOKALAEMIC METABOLIC ALKALOSIS + impaired glucose tolerance.
Ectopic ACTH e.g. secondary to small cell lung cancer = low potassium.
Overnight low dose dex suppression test = first line. Patients WITH Cushing’s will not have their morning cortisol spike suppressed.
24hr urinary free cortisol (2 measurements)
Bedtime salivary cortisol (2 measurements)
High dose dex suppression test, measuring cortisol and ACTH.
Pathophysiology of Addison’s disease:
Autoimmune destruction of adrenals, causing reduced cortisol and aldosterone.
Management of a) Addison’s disease + investigations b) Cushing’s disease.
Addison’s - short Synacthen test to measure plasma cortisol before and after synthetic ACTH. Also adrenal autoantibodies to 21-hydroxylase may be present. Also ?9am serum cortisol sample, if <100 definitely abnormal.
Hydrocortisone in 2 or 3 divided doses, majority in first half of the day, and fludrocortisone (double hydrocort in illness, fludro same.)
Cushing’s - dependent on cause e.g. trans-sphenoidal removal if pit adenoma, surgical adrenal tumour or ectopic ACTH tumour e.g. lung.
?Remove both adrenals and life long replacement.
Difference between Cushing’s disease and Cushing syndrome:
Cushing disease = pituitary adenoma secreting ACTH, stimulating excessive cortisol release from the adrenals.
Cushing syndrome has other causes including prolonged courses of exogenous corticosteroids.
Causes of hyponatraemia, split into urinary sodium <20 and >20mmol, depending on volume status:
Water excess or sodium depletion. Take into context with urinary sodium and osmolality.
https://handbook.ggcmedicines.org.uk/media/1099/195-hyponatraemia-flowchart-1-final-200717e.pdf
Causes of hypernatraemia:
Dehydration
Excessive IV saline
Diabetes insipidus
Very careful when correcting, can lead to cerebral oedema; brain tissue can lose sodium and potassium rapidly, lowering of other things e.g. water goes slower.
Should correct at 0.5mm/hour
What is serum osmolality?
Measure of the number of osmotically active particles in 1kg of serum.
Can help differentiate between hypertonic, hypotonic (true) or osmolar hyponatraemia (pseudo due to e.g. lipids and paraproteins in blood)
What is the diagnostic criteria for PCOS called?
Rotterdam criteria
Explain insulin resistance in PCOS
Lack of response to insulin hormone, results in high blood sugar levels.
Can present with acanthosis nigricans.
4 types of thyroid cancer:
Papillary , young females, good prognosis
Follicular
Medullary - parafollicular C cells, secrete calcitonin, MEN2
Anaplastic - hashimoto’s thyroiditis
Discuss the cancers present in MEN 1 and MEN 2a/b.
MEN1 = 3Ps
Parathyroid, Pituitary, Pancreas *(insulinoma, gastrinoma recurrent peptic ulceration)
Most common presentation = hypercalcaemia.
MEN2a = 2Ps + Medullary thyroid
Parathyroid, Phaeo,
RET oncogene.
MEN2b = 1P = phaeo + medullary thyroid.
Marfanoid body habitus, neuromas.
RET oncogene
Function of the parathyroid gland / parathyroid hormone:
PTH is produced in response to low calcium and acts to raise it.
Bones –> increase osteoclast activity, releasing calcium and phosphate, raising serum calcium and phosphate.
Kidneys –> distal tubule (stimulate calcium reabsorption), proximal tubule (decreases phosphate reabsorption, more free calcium as less phosphate for it to bind to), stimulates kidney to convert vit d to active form calcitriol which acts to increase absorption from SI, kidneys and provides negative feedback
Symptoms of hyperparathyroidism.
80% of patients are asymptomatic.
Bones stones abdominal groans, psychic moans
Associated with hypertension
Symptoms of hypoparathyroidism, + investigation results and main cause.
Main symptoms of hypoparathyroidism are secondary to hypocalcaemia (see previous hypocalcaemia card).
PTH reduced e.g. secondary to thyroid surgery.
LOW CALCIUM, high phosphate.
Treated with alfacalcidol.
Biochemical / hormonal results in primary vs secondary vs tertiary hyperparathyroidism:
PTH elevated in all (obviously)
Primary
Calcium high
Phosphate low
Urine calcium:creatinine >0.01
Solitary adenoma 80%
Secondary
Calcium low or normal
Phosphate high
Vitamin D low
Hyperplasia due to low calcium in CHRONIC RENAL FAILURE
Tertiary
Calcium normal or high
Phosphate decreased or normal
Vit D normal or decreased
ALP elevated
Hyperplasia due to correction of underlying renal disease e.g. transplant, all 4 glands.
Biochemical / hormonal results in hypoparathyroidism:
PTH reduced
Low calcium
High phosphate
Treat with alfacalcidol
What is monogenic diabetes?
MODY most common form.
AD inheritance, impairment in insulin secretion but NOT insulin action.
Not driven by lifestyle factors.
MODY3 is most common.
Presentation of monogenic diabetes / MODY:
Younger patients
Mild, non-ketotic hyperglycaemia, persistent, asymptomatic
Only DKA if severe illness.
Normal weight
No signs of insulin resistance
<25
Klinefelter’s causes hypogonadism. What is the chromosomal abnormality present, and what are the clinical features?
47XXY
Taller than average
Lack of secondary sexual characteristics
Small, firm testes
Infertility
Gynaecomastia alongside increased incidence of breast cancer
Gonadotrophin levels raised but LOW testosterone
What does a phaeochromocytoma secrete, and which genetic syndromes may it be associated with?
Catecholamines
Von Hippel Lindau
MEN II
Neurofibromatosis
3 10%s of phaeochromocytoma, what are they?
10% bilateral
10% extra-adrenal (adjacent to aortic bifurcation)
10% malignant
Clinical features of a phaeochromocytoma, and the main clinical test:
HYPERTENSION
tachycardia, palpitations
headaches
sweating
anxiety
24 urinary metanephrines 97% sensitivity
Surgery is the definitive management of a phaeochromocytoma, however they must first be stabilised with medical management to reduce anaesthesia and surgical risks. What medical management is indicated?
Alpha blockers first e.g. phenoxybenzamine
Beta blockers e.g. propranolol
Prevents haemodynamic instability in surgery.
Why are urinary metanephrines the test of choice compared to serum catecholamine or adrenaline level, and compared to urinary catecholamines?
Serum catecholamine or adrenaline fluctuates a lot and only has a very short half life.
Metanephrines have longer half life and more stable levels.
Imaging to look for a phaeochromocytoma?
CT or MRI
What is Conn’s syndrome?
Primary hyperaldosteronism caused by an adrenal adenoma.
What is the most common cause of primary hyperaldosteronism?
Bilateral idiopathic adrenal hyperplasia
Discuss the normal function of aldosterone including where it is secreted from and where it exerts it’s action, and what triggers it’s release.
Aldosterone = mineralocorticoid secreted from adrenal gland.
It increases sodium reabsorption, and potassium secretion from the distal tubule (SAVES SALT).
Increases hydrogen secretion from the collecting ducts.
More fluid is retained in the body, increases intravascular volume and BP.
3 other causes of primary hyperaldosteronism.
Unilateral hyperplasia
Familial hyperplasia
Adrenal carcinoma
Clinical features of primary hyperaldosteronism:
HYPERTENSION and hypokalaemia (muscle weakness, more common with adrenal adenomas).
Metabolic alkalosis (aldosterone increases hydrogen secretion from collecting ducts).
Indications for suspicion of primary hyperaldosteronism, and first line investigation?
Hypertension with hypokalaemia
Hypertension resistant to treatment
Plasma aldosterone/renin ratio = HIGH ALDOSTERONE with LOW RENIN
Positive plasma aldosterone / renin ratio shows high aldosterone levels alongside low renin; why does this happen, and what further investigations are warranted?
Renin is low due to negative feedback on the JG cells due to the high sodium.
High resolution CT abdomen and adrenal vein sampling (unilateral vs bilateral sources of aldosterone excess)
Management of an adrenal adenoma vs. bilateral adrenocortical hyperplasia:
Adrenal adenoma = laparoscopic adrenalectomy
Bilateral adrenal hyperplasia = aldosterone antagonist e.g. spironolactone
