Endocrine Flashcards
Causes of hypoglycaemia?
Too much insulin, too much exercise, too little carbohydrates or combination. Alcohol Sulphonylureas Adrenal failure Liver failure Hypopituitarism Infection
Patients with DM secondary to total pancreatectomy more susceptible
What is C-peptide?
Low C-peptide = exogenous insulin
High C-peptide = endogenous insulin
Treatment of hypo if able to swallow?
Glucotabs/Glucogel, lucozade
Rpt CBG in 10-15 mins - repeat up to x3 if low
If no improvement –> IV glucose/IM glucagon
Management of hypo if unconscious?
75-100ml 20% glucose OR
150-200 ml 10% glucose over 15 mins
or IM glucagon 1mg
What to give after a hypo?
Continuous infusion of 10% glucose for 8hrs if due to insulin/sulphonylurea
Once CBG >4, long acting carbs/normal meal
CONTINUE NORMAL INSULIN DOSES
How long no driving after hypo?
45 mins
Diagnostic criteria for DKA?
Hyperglycaemia (>11mmol/L)
Acidosis (venous pH <7.3 or bicarb <15mmol/L)
Blood ketones >3mmol/L or ketonuria (>++)
When to give K+ in DKA?
Add potassium supplementation (40mmol/L after 1st bag) – max 2L.
Still give if K+ normal - only withhold K+ if >5.5 – if <3.5, GET HELP – need a central line.
Rate of infusion in DKA?
Fixed rate insulin IV infusion - 0.1 unit/kg/hr IV over a sliding scale.
50 units human soluble insulin e.g. Actrapid in 50ml 0.9% saline)
When to monitor ketones, K+ and pH in DKA?
Monitor glucose and ketones hourly, and venous HCO3-, K+ and pH at 60 min and 2 hourly thereafter; K+ will fall unless replaced.
When to stop insulin infusion in DKA?
Continue insulin infusion until ketones<0.3mmol/L and pH >7.3.
At this point convert to regular SC insulin if eating and drinking normally, otherwise using a sliding scale
Continue long acting insulin in DKA?
YES
Prevents rebound hyperglycaemia when IV stopped. Short-acting insulin stopped until about to discontinue IV
Diagnosis of T1DM?
Symptoms plus…
Random venous blood glucose >11.1 OR Fasting venous blood glucose >7.0 OR OGTT
If asymptomatic, need 2 separate results
Symptoms of diabetes?
Thirst, toilet, thinner, tired
Infections - skin, UTI, candida genital infections
HbA1c to diganose TIIDM?
48 mmol/mol
HbA1c targets in TIIDM?
Lifestyle/monotherapy - 48 mmol/mol
Hypo-associated drug - 53 mmol/mol
Dual therapy/triple therapy/insuline - 53 mmo/mol
Name, mechanism, benefits/disadvantages of biguanides?
Metformin
Decreases glucose production by liver and increases insulin sensitivity of body tissues.
Doesn’t put on weight or cause hypos, but causes bowel problems.
Not indicated if eGFR <35.
Name, mechanism, benefits/disadvantages of Sulfonylureas?
Gliclazide, glimepiride
Depolarises pancreatic beta cells, which opens voltage gated Ca2+ channels, leading to increased secretion of insulin.
Causes weight gain. Better than metformin at reducing blood glucose quickly – good if patient experiencing symptoms.
Name, mechanism, benefits/disadvantages of DDP-4 inhibitors?
Sitagliptin, alogliptin, linaliptin
Inhibits enzyme which breaks down incretin, which is released in response to oral glucose - ↓incretin –> ↓glucagon –> ↑insulin.
Linagliptin safe in renal impairment.
Name, mechanism, benefits/disadvantages of Thiazolidinediones?
Pioglitazone
Reduces insulin resistance in the liver and peripheral tissues, decreases gluconeogenesis in the liver –> reduces blood glucose.
Contraindicated in heart failure, hepatic impairment, DKA, history of bladder cancer, uninvestigated macroscopic haematuria.
Name, mechanism, benefits/disadvantages of SGLT2 Inhibitor?
Dapagliflozin, canagliflozin, empagliflozin
Inhibits reabsorption of glucose in the kidney –> lower blood sugar because peeing out glucose.
Can cause weight loss because of lost calories, but can cause UTI/thrush.
Name, mechanism of GLP-1 agonist?
Liraglutide, exendatide
Works on same pathway as DPP-4 inhibitors but are more potent.
Screening in TIIDM?
Retinopathy – screening programme
Foot problems – annual foot check
Nephropathy – annual screening (Urine ACR and eGFR)
Cardiovascular Risk Factors
Age, albuminuria, smoking status, blood glucose control, blood pressure, full lipid profile
What causes Grave’s disease?
IgG against TSH receptor
Process also directed towards soft tissues in the orbit –> inflammation and swelling
What is Grave’s associated with?
T1DM, Addison’s, Coeliac etc
Signs specific to Grave’s disease?
- Eye disease – exophthalmos, opthalmoplegia, swelling around the eyes (congestive opthalm-something)
- Pretibial myxoedema – odematous swellings above lateral malleoli.
- Thyroid acropachy – extreme manifestation, with clubbing, painful finger and toe swelling and periosteal reaction in limb bones
Complications of Grave’s disease?
Heart failure (thyrotoxic cardiomyopathy), angina, AF, osteoporosis, opthalmopathy, gynaecomastia.
Blood results in Grave’s disease? Other investigations?
TSH↓ (suppressed), T3 and T4↑
May be mild normocytic anaemia, mild neutropenia (Grave’s), ESR↑, Ca2+↑, LFT↑
Thyroid receptor antibody (TRAB), USS (if nodule –> possible Ca)
Drug management of Grave’s disease?
Symptomatic treatment = Beta-blockers
Long-term treatment = Antithyroid drugs
Carbimazole – for short-term control or to achieve remission. 18 months treatment usually recommended
Giving carbimazole and levothyroxine together reduces the risk of iatrogenic hypoT.
Surgical management of Grave’s disease?
Thyroidectomy
Risk of damage to recurrent laryngeal nerve/ hypoparathyroidism
Most become hypothyroid
Radioiodine management of Grave’s disease?
Increasingly 1st line - most become hypoT after treatment
Contraindicated in pregnancy and lactation
Causes of hypothyroidism?
Primary atrophic - no goitre
Hashimoto’s thyroiditis - goitre
Iodine deficiency, post thyroidectomy or iodine, drug induced, subacute thyroiditiis (temporary hypo after hyper phase)
Signs of hypothyroidism?
BRADYCARDIC
Bradycardia Reflexes relax slowly Ataxia (cerebellar) Dry thin hair/skin Yawning/drowsy/coma Cold hands Ascites Round puffy face/double chin/obese Defeated demeanour, Immobile + ileus CCF
Peaches and cream complexion
Management of hypothyroidism?
Levothyroixine
If IHD, start low and titrate dose upwards.
Treatment usually lifelong.
What does Addison’s result in the deficiency of?
Mineralocorticoids (aldosterone)
Glucocorticoids (cortisol)
Androgens (testosterone, DEHA)
Symptoms of Addison’s?
GENERAL = Fatigue, muscle weakness/pain
CVS = Hypotension (postural) –> dizziness and headache
GI = Anorexia, weight loss, N+V, intermittent abdo pain, salt craving
Decrease in pubic/axillary hair, depression, impotence/ amenorrhoea, hypoglycaemia, depression
Signs of Addison’s?
Skin pigmentation (due to high ACTH)
Dull, grey-brown colouration - exposed skin, pressure areas, palmar creases, knuckles, buccal mucosa, recent scars
May be associated with vitiligo –> patchy appearance
Triggers of Addisonian crisis?
Trauma
Severe hypotension
Sepsis
Presentation of addisonian crisis?
Intensification of pre-existing symptoms, especially nausea, vomiting, epigastric pain Fever Lethargy Hypotension Hypovolaemic vascular shock
Management of Addisonian crisis?
Management = rapid elevation of circulating glucocorticoid and replacement of salt and glucose loss
GP – hydrocortisone 100mg IM –> hospital
IV fluids
Oral replacement once stable
Blood results in Addisons?
↓Na+, ↑K+/H+ - due to low aldosterone
↑Urea/albumin – due to dehydration
↑Serum renin – due to sodium depletion
Diagnosis of Addison’s?
Serum Cortisol levels - (8-9am)
If between 100-400 nanomol/L –> refer to specialist for short synacthen test
Management of Addison’s long term?
Treat cause + replace glucocorticoid and mineralocorticoid + education.
- MedicAlert bracelet and steroid card
- Hydrocortisone (10mg/M2 per day), fludrocortisone (0.1-0.3 mg/day) and dehydropiandrosterone (DHEA) daily
- Screen for other autoimmune diseases (thyroid)
Requires lifelong treatment.
Features of diabetic foot disease?
Microangiopathy –> peripheral neuropathy
Sensory = decreased awareness of injury
Motor = distortion of weight bearing characteristics of foot
Autonomic = disruption of control of vascular supply/sweating
Actions of PTH?
2 ACTIONS ON KIDNEY, 1 ON BONE (high calcium, low phosphate)
Increases reabsorption of Ca2+ by kidney
Increases renal-1-hydroxlyase –> produces calcitirol (active form of vitamin D) –> more absorption from gut
Stimulates osteoclast activity –> release calcium from bone
What is primary hyperparathyroidism?
One or more parathyroid glands produce excess PTH – 80% = solitary adenoma.
What is secondary hyperparathyroidism? (most common)
PTH secreted excessively in response to prolonged ↓Ca2+ and phosphate levels (due to kidney, liver or bowel disease) – chronic renal failure/malabsorption/vitamin D deficiency.
What is tertiary hyperparathyroidism?
Autonomous secretion of PTH as a result of longstanding CKD (hyperplastic change of glands).
Biochemistry of primary/ secondary/tertirary hyperparathyroidism?
Primary = ↑PTH, ↑Ca2+
Secondary = ↑PTH, ↓Ca2+
Tertiary = ↑↑PTH, ↑Ca2+ + Renal Failure
Management of primary hyperparathyroidism?
Increase fluid intake to prevent stones and avoid thiazides/high Ca2+ and phosphate intake
Excision of adenoma if complications
Cinacalet - increases sensitivity of PT glands to Ca2+
Management of secondary hyperparathyroidism?
Phosphate binders/vit D
Cinacalcet/parathyroidectomy
Cancers that cause hypercalcaemia?
NSCLC (squamous cell) Breast Renal cell Multiple myeloma and lymphoma H+N cancers
How do cancers cause hypercalcaemia?
Transforming growth factor alpha - stimulates bone resorption
PTH related peptides - mimics PTH
Features of hypercalcaemia?
Cats go numb with a short QT
Confusion, arrhythmia, tetany, numbness, long QT
(Bones, stones, moans, groans)
Classification of hyperlipidaemia?
Primary - high LDL only
Familial - LDL receptor defects
Secondary - cushing’s, hypoT, nephrotic syndrome, cholestasis
Mixed - high LDL and triglycerides, caused by T2DM, metabolic syndrome, alcohol abuse and CKD
Target for reducing cholesterol?
40% reduction in non-HDL cholesterol after 3 months
Most common cause of hypoparathyroidism?
Destruction during surgery
Others = primary (idiopathic/congenital), DiGeorge syndrome, infiltration by iron (haemochromatosis, mets)
Hypomagnasaemia (Mg is necessary for PTH secretion)
Vitamin D excess
What is pseudohypoparathyroidism?
Failure of target cells to respond to PTH (autosomal dominant - rare)
Results in hypoparathyroidism?
Low calcium, high phosphate
Normal alk phos, low PTH
Risk factors for thyroid cancer?
Radiation to neck area Radioiodine treatment Deficiency and excess dietary iodine Prolonged stimulation with TSH (can be due to iodine deficiency) Chronic lymphocytic thyroiditis
Types of thyroid cancer?
Papillary adenocarcinoma (80%), follicular adenocarcinoma (10%), medullary adenocarcinoma (5%), anaplastic carcinoma (3%), thyroid lymphoma (1%)
Presentation of thyroid cancer?
Rapidly growing hard thyroid mass
Lymphadenoapthy
Indicators of extrathyroidal invasion (hoarseness, dysphagia)
History of ionising radiation/family history of thyroid cancer
What is a multinodular (toxic) goitre?
2nd most common cause of hyperT after Grave’s
Functionally autonomous thyroid nodules produce T3/T4
Cause of multinodular goitre?
Iodine deficiency –> reduced T4 production –> thyroid cell hyperplasia
Predisposes to mutation in TSH receptor
If receptor is constitutively active, becomes toxic and produces excess T3/T4.
What is a toxic nodule?
Benign tumour of thyroid gland - usually follicular adneoma.
Neoplasm resulting from a single cell
Toxic nodule on examination?
Solitary, spherical, encapsulated lesion that is well demarcated from surrounding parenchyma. 3cm diameter on average.
Complications of a simple (non toxic) goitre?
Dysphagia
Vocal changes
Dyspnoea
Facial congestion
Types of thyroiditis?
Hashimoto’s (autoimmune) thyroiditis
De Quervains (subacute granulomatous thyroiditis)
Subacute lymphocytic/ painless thyroiditis
Riedel’s thyroiditis
What is autoimmune thyroiditis?
Most common cause of hypothyroidism in non-iodine deficient areas.
Autoimmune –> extensive infiltration of the thyroid parenchyma by lymphocytes and plasma cells, with the formation of germinal centres.
Examination findings in thyroiditis?
GOITRE + HYPOTHYROIDISM
Thyroid firm, well defined with enlarged pyramidal lobe and palpable neighbouring lymph nodes.
Enlargement slow and painless, but rarely may be more rapid and painful
Progression of visual field defects in pituitary adenoma?
Superior bi-temporal quadrantanopia progressing to bi-temporal hemianopia
What is Pheochromocytoma?
Functional neuroendocrine tumour that arises from chromaffin cells in adrenal medulla – secretes a high amount of catecholamines
Usually adrenaline/noradrenaline - can also secrete dopamine and ACTH
Symptoms of Pheochromocytoma?
Hypertension –> hypertensive crisis (can be triggered by any stressor)
Headache, palpitations, tachycardia, sweating, anxiety, panic attacks, tremor, N+V, fever
Prolonged –> CCF + Pulmonary oedema
Diagnosis of Pheochromocytoma?
24 hour collection of urinary catecholamines
Imaging to localise tumour (CT/MRI)
Management of Pheochromocytoma?
Alpha blockers until definitive surgery
Situations to consider Pheochromocytoma?
Hypertensive with orthostatic hypotension and tachycardia
Hypertensive whose symptoms respond poorly to anti-hypertensive treatment
Patient whose blood pressure fluctuates widel
Hypertensive with cafe au lait spots
What is Cushing’s syndrome?
Clinical state produced by chronic glucocorticoid excess and loss of the normal feedback mechanisms of the hypothalamo-pituitary-adrenal axis and loss of circadian rhythm of cortisol secretion
ATCH dependent causes of Cushing’s syndrome?
CUSHING’S DISEASE
Bilateral adrenal hyperplasia from an ACTH-secreting pituitary adenoma. Does not respond to dexamethasone suppression test.
ECTOPIC ACTH PRODUCTION
SCLC/carcinoid tumours pigmentation (due to ↑↑ACTH), hypokalaemic metabolic alkalosis (↑↑cortisol leads to mineralocorticoid activity), weight loss, hyperglycaemia
ACTH-independent causes of Cushing’s syndrome?
IATROGENIC (most common)
Long term steroids
ADRENAL ADENOMA, ADRENAL NODULAR HYPERPLASIA
No suppression with dexamethasone because tumours/nodules are autonomous
Symptoms of Cushing’s syndrome?
Weight gain
Mood change (depression, lethargy, irritability, psychosis)
Proximal weakness
Gonadal dysfunction (irregular menses, hirsutism, erectile dysfunction)
Acne
Recurrent Achilles tendon rupture
Occasionally virilisation if female
Signs of Cushing’s syndrome?
Central obesity
Plethoric moon face
Buffalo neck hump
Supraclavicular fat distribution
Skin and muscle atrophy, bruises, purple abdominal striae
Osteoporosis, ↑BP, ↑glucose, infection-prone, poor healing
How is congenital adrenal hyperplasia (adrenogenital syndrome) inherited?
Autosomal recessive inheritance
Pathophysiology of congenital adrenal hyperplasia?
Enzyme deficiency leading to…
- Deficient cortisol/ aldosterone production
- Excess precursor steroids
Features of congenital adrenal hyperplasia?
Virilisation (females)
Hyperpigmentation (males - scrotum)
Tall stature/precocious puberty (males)
Adrenal crisis (in first days of life)
What happens if you have to much aldosterone secretion?
Hypokalaemia (excretion of K+)
Metabolic alkalosis (excretion of H+)
HTN (retention of Na+ and H2O)
Primary cause of Hyperaldosteronism?
CONN’S SYNDROME
High aldosterone levels in absence of activation of RAAS
Can be caused by adrenal adenoma (majority), bilateral adrenal nodular hyperplasia and adrenal carcinoma
Secondary causes of Hyperaldosteronism?
High levels of aldosterone are present as a result of activation of the RAAS
Causes = diuretic therapy, accelerated HTN, CCF, nephrotic syndrome, liver cirrhosis with ascites, renal artery stenosis, bronchial carcinoma (rare)
Presentation of Hyperaldosteronism?
Asymptomatic
Mild HTN, lethargy, muscular weakness, polyuria/polydipsia, persistent hypokalaemia, intermittent paraesthesiae, tetany and occasionally paralysis.
Sodium usually mildly elevated or normal.
Main cause of hirsutism?
PCOS
Pathophysiology of PCOS?
Disordered LH production and peripheral insulin resistance with compensatory raised insulin levels –> raised ovarian androgen production.
↑Insulin –> ↑adrenal androgen production
Increased intraovarian androgens –> excess follicles and absent/irregular ovulation
↑Peripheral androgens –> hirsutism
Consequences of PCOS?
At risk of TIIDM, endometrial cancer (unopposed oestrogen due to amenorrhoea), but normal oestrogen levels so not at risk of osteoporosis
Why does obesity worsen PCOS?
Increasing body weight –> increased insulin –> increased androgen levels
Investigations in hirsutism?
Measure early morning plasma total testosterone
Pelvic USS (is suspicion of PCOS)
Pregnancy test (if amenorrhoea)
LH/FSH, prolactin, TFTs etc.
Treatment of hirsuitism?
Physical hair removal
Weight loss
Anti-androgens (cyproterone acetate/ spironolactone), oestrogen, GnRH analogues, glucocorticoids, metformin (in PCOS)
Topical eflornithine
Features of HHS?
Hypovolaemia
Marked hyperglycaemia (30 mmol/L or more) without significant hyperketonaemia (pH 7.3, bicarbonate >15 mmol/L)
Osmolality usually 320 mosmol/kg or more
When is ADH released?
In response to…
- Decrease in plasma volume
- Increase in serum osmolality
Opens aquaporins in DCT –> water flows back into circulation
What is diabetes insipidus?
Passage of large volumes of dilute urine due to…
- Deficiency of ADH (cranial)
- Renal resistance to ADH (nephrogenic)
Causes of cranial diabetes insipidus?
RARE
Alcohol (lol)
idiopathic, congenital, pituitary tumour, trauma
Infiltration (histiocytosis, sarcoidosis)
Vascular (haemorrhage – sheehan’s syndrome),
Infection
Causes of nephrogenic diabetes insipidus?
Inherited
Metabolic (↓K+, ↑Ca2+ - hypercalcaemia causes polyuria and polydipsia),
Drugs (lithium, demeclocycline)
CKD
Post-obstructive uropathy
Symptoms of diabetes insipidus?
Polydipsia, polyuria, nocturia
Confusion/coma if hypernatraemia (esp in cranial DI)
Investigations in diabetes insipidus?
↑Na+
Plasma osmolality rasied
Urine osmolality low
Definitive diagnosis in diabetes insipidus?
Fluid deprivation test - give desmopressin, measure urine osmolality over 12 hours
Cranial - will be able to concentrate urine
Nephrogenic - won’t be able to concentrate urine
Investigations if TOO MUCH hormone
Measure at nadir
Try to suppress
Evaluate their 24 hour secretion
Measure preceding hormone (elevated T4, measure TSH)
Investigations if TOO LITTLE hormone
Measure at peak
Try to stimulate
Measure preceding hormone (Elevated free T4, measure TSH)
Determining aetiology of endocrine problems
Supplementary hormone tests
Immunology
Radiology/nuclear medicine
Hyperpigmentation in Addison’s?
Melanocyte-stimulating hormone (MSH) and ACTH share the same precursor molecule, pro-opiomelanocortin (POMC).
After production in the anterior pituitary gland, POMC gets cleaved into gamma-MSH, ACTH, and beta-lipotropin. The subunit ACTH undergoes further cleavage to produce alpha-MSH, the most important MSH for skin pigmentation. In secondary and tertiary forms of adrenal insufficiency, skin darkening does not occur, as ACTH is not overproduced.
Criteria for treating hypothyroid?
TSH >4, TPO +ve or TSH >10 TPO -ve
Side effects of carbimazole?
Rash
Itch
GI upset
Agranuloctyosis (one to worry about)
MEN1?
Parathyroid, pancreas, pituitary
MEN2?
Phaeochromocytoma
Papillary cell carcinomas
Paratyhroid
What does Mg deficiency do?
Inhibits PTH secretion –> hypocalcaemia
Magnesium deficiency caused by PPIs
Causes of hypercalcaemia?
Hyperparathyroidism
Malignancy
Granulomatous disease (TB and Sarcoidosis)
Familial Hypocalciuric Hypercalcaemia
Drugs (thiazides, lithium, vit D excess)
Thyrotoxicosis/Addison’s
Features of acute hypoadrenalism diagnostic features?
Hyperpigmentation (primary)/Hypopigmentation (secondary) Hypovolaemic collapse Typical electrolyte changes Other hormone abnormalities Physical examination
Features of secondary adrenal failure?
Bitemporal hemianopia
Hypopigmentation
