Endocrinology and metabolism Flashcards

1
Q

Type 1 Diabetes

A

T1DM, 0.6% UK population
- autoimmune destruction of pancreatic Beta cells, so insulin not produced, ‘starving in the midst of plenty’ - glucose levels are high but the body cannot use or store it

Presentation (typically age 5-15)
- polyuria
- polydipsia
- weight loss
(or in DKA)
\+ long term retinopathy, nephropathy, neuropathy, macrovascular complications
  • see autoantibodies GAD, IA-2, Tyrosine-phosphatase like molecule, ZnT8
  • fasting plasma glucose of >6.9mmol/L
  • random plasma glucose of >11.1mmol/L
  • HbA1c >48mmol/L
  • risk from genetics, geography, childhood infection

Mx

  • education! LIFELONG AND RISKY
  • diet - weight loss, low bp, low lipid profile
  • SC insulin to maintain blood glucose 3.9-6mmol/L and HbA1c <53
  • ACEi to control bp
  • statins to control lipids
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2
Q

Type 2 Diabetes

A

T2DM, 5% of the UK population and rising fast
- obesity -> insulin insensitivity -> exhausted pancreas -> insulin deficiency

Presentation
- often asymptomatic, through screening
- but can get polyuria, polydipsia, weight loss in hyperglycaemia
+ candida infections, cellulitis, UTIs
(or present in HHS)
+ long term retinopathy, nephropathy, neuropathy, macrovascular complications

  • fasting plasma glucose of >6.9mmol/L
  • random plasma glucose of >11.1mmol/L
  • HbA1c >48mmol/L
  • risk from age, obesity, gestational diabetes, fhx, ethnicity, HTN, PCOS

Mx

  • conservative - education, diet and exercise, smoking cessation
  • medical - ACEi bp control, statins, metformin (biguanides) to increase insulin sensitivity, insulin in late stage
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3
Q

Thyrotoxicosis presentation, causes and risk factors

A

= condition when excess thyroid hormone
- usually caused by Grave’s - diarrhoea, exopthalmos, fatigue, fine tremor, goitre, heat intolerance, non-pitting oedema, palpitations, unintentional weight loss
Beware thyroid storm presenting as above but in severe emergency!

Caused by

  • Grave’s disease 10x more in females, more in smokers and if autoimmune history (autoimmune activation of TSH receptor)
  • Toxic multinodular goitre more in iodine deficiency, older age, head and neck irradiation (autonomously functioning (hot) nodules independent of TSH control, + cold nodules with potential for cancer)
  • Toxic thyroid adenoma more in iodine deficiency, young adulthood (single large thyroid nodule)
  • Post partum thyroiditis - don’t give thyroid blocking meds!
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4
Q

Investigations and management of thyrotoxicosis

A

Ix

  • low TSH
  • high free T4 and T3
  • elevative radioactive iodine uptake
  • TSH receptor antibodies +ve in Grave’s
  • TPO antibody suggests autoimmune
  • thyroid USS (enlarged diffuse vascular in Grave’s, nodules if not)

Mx

  • Grave’s - anti-thyroid drug therapy carbimazole (beware bone marrow supression) or symptomatic therapy (eg propanolol, prednisolone)
  • toxic multinodular goitre - radioactive iodine therapy
  • for all - surgery if retrosternal and compressing trachea or oesophagus
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5
Q

Hypothyroidism presentation, investigations and management

A

Presentation - weakness, lethargy, depression, weight gain, constipation, cold intolerance, menstrual irregularity, dry skin/eyes, bradycardia, outer eyebrow loss
- 8x more in females, peak age 30-50

Investigations

  • low serum T4
  • serum TSH raised in primary, lowered in secondary hypothyroidism
  • TPO (antithyroid peroxidase antibody) raised suggests autoimmune

Management
- daily levothyroxine (don’t over-treat)

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6
Q

Causes of hypothyroidism

A

Primary (95%)

  • thyroid not making enough T3/4, raised TSH to try and stimulate it
  • primary atrophic
  • Hashimoto’s (with goitre, often other autoimmune problems also)
  • post-thyroidectomy or radio-iodine treatment
  • drug induced - antithyroid drugs, amiodarone, lithium, iodine

Secondary (5%)
- not enough TSH

Risk factors
- female, middle aged, fhx of autoimmune disorders, radiotherapy to head and neck, Turner’s/Down’s syndromes, MS, iodine deficiency, drugs

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7
Q

Primary hyperparathyroidism

A
  • too much PTH -> hypercalcaemia

Presentation

  • osteoporosis, bone pain
  • kidney stones
  • paraesthesia, muscle cramps
  • poor sleep, fatigue, anxiety, depression

Caused by
- parathyroid adenomas (85%)
- inherited - multiple endocrine neoplasia, HPT-jaw tumour syndrome
- rarely malignancy
Risk factors - female, age 50-60, fhx, lithium treatment

Investigations

  • raised serum calcium
  • raised PTH

Treatment
- parathyroidectomy if symptomatic, monitor if not

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8
Q

Secondary hyperparathyroidism

A
  • hypocalcaemia -> reactive raise in PTH

Presentation

  • bone pain
  • paraesthesia, muscle cramps
  • Chvostek’s and Trousseau’s sign

Caused by

  • CKD (almost all dialysis dependent patients get)
  • vitamin D deficiency
  • malabsorption diseases

Investigations

  • low serum calcium
  • raised serum PTH
  • check eGFR

Management

  • treat cause (sunlight, active vit D/calcium supplementation)
  • if untreated, will lead to tertiary hyperPTH where even if you resolve cause the parathyroid will continue to be overactive
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9
Q

Cushing’s syndrome

A

= clinical manifestation of pathological hypercorticolism (from any cause)

Signs

  • weight gain (central obesity, moon face
  • proximal muscle weakenss
  • thinned skin, bruising
  • striae
  • HTN
  • glucose intolerance/DM
  • osteopenia

Causes

  • usually exogenous steroid use
  • endogenous - Cushing’s disease (ACTH-secreting pituitary tumour), ectopic ACTH tumour, adrenal adenoma, adrenal carcinoma

Ix

  • elevated glucose
  • late night salivary cortisol
  • low dose dexamethasone suppression test (remains elevated)
  • 24hr urinary free cortisol

Mx
- remove cause if tumour/drugs

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10
Q

Addison’s disease

A

= primary adrenal insufficiency
RARE (12x more in F>M)

Presentation
- fatigue
- anorexia + weight loss
- hyperpigmentation (gums)
\+ nausea, vomiting, hypotension

90% due to autoimmune, or sometimes TB or other infections

  • primary = adrenal gland dysfunction
  • secondary = inadequate ACTH
  • tertiary = inadequate CRH

Ix

  • electrolytes - low Na, high K (lack of aldosterone)
  • low morning serum cortisol
  • low ACTH stimulation test

Mx
- hormone replacement - glucocorticoid (hydrocortisone), mineralocorticoid (fludrocortisone), androgen replacement (DHEA)

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11
Q

Hyperprolactinaemia

A

= abnormally high levels prolactin >20 men, >18 women

Women - galactorrhoea, disrupted menstrual cycle (infertility)

Men - hypogonadism (infertility), erectile dysfunction

Due to excess TRH (from hypothalamus), too little dopamine, excess prolactin
- caused by breastfeeding, stress, pituitary prolactinoma, drugs, hypothyroidism
(this then inhibits GnRH)

Investigations - blood prolactin, thyroid function, MRI for pituitary tumour
Management - dopamine agonists

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12
Q

Diabetic ketoacidosis

A

In T1DM - hyperglycaemia, acidaemia, ketonaemia

Presentation
- polyuria, polydipsia, weakness
- nausea + vomiting, abdo pain, Kussmaul respiration, acetone breath, reduced GCS
+ volume depletion signs - dry, tachycardia, hypotension, coma

Triggers

  • lifestyle - skipping meals/alcohol
  • infection
  • stressors eg MI/stroke/trauma
  • first presentation diabetes
  • drugs eg steroids, thiazides, sympathomimetics

Ix

  • ABG and bloods - high glucose, low pH, low bicarb, raised ketones, raised K+?, raised anion gap
  • urinalysis

Management

  • REHYDRATE
  • REPLACE INSULIN ( 0.1 units/kg/hour, + dextrose alongside saline)
  • POTASSIUM (will drop as give insulin so may need to replace OR reduce)
  • TREAT CAUSE
  • stop short acting insulin, continue long acting dose
  • MONITOR (hourly potassium and VBG and cap ketones)
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13
Q

Hyperosmotic Hyperglycaemic Syndrome

A

= HHS, = hyperosmolar non-ketotic coma

  • in T2DM, where profound hyperglycaemia and volume depletion (NO ketoacidosis)
  • slower onset than DKA, over days-weeks
  • polyuria, polydipsia, weight loss, weakness, altered mental state
  • rare, but high mortality (occurs in older comorbid T2DM)
  • usually precipitated by infection, acute illness, inadequate diabetic therapy, dehydration

Ix

  • plasma glucose >33.3
  • urea rise
  • Na+ reduce, K+ rise
  • osmolality rise
  • anion gap normal (no ketoacidosis)
  • ECG (potassium)
  • creatinine rise (AKI from dehydration)

Mx

  • rehydration (IV fluid)
  • IV insulin
  • treat and monitor potassium
  • treat underlying cause
  • stop nephrotoxic meds
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14
Q

Hypoglycaemia

A

<3.3mmol/L
Can be non-diabetic!

Presentation

  • sweating, shaking, palpitations, anxiety
  • confusion, aggression, seizures, coma
  • Whipple’s triad = hypo symptoms + low plasma glucose + resolution of symptoms after raising glucose

Causes

  • iatrogenic (excess insulin or sulphonylurea)
  • GH (pituitary) deficiency/adrenal insufiency
  • insulinoma
  • simple reactive hypoglycaemia

Mx

  • oral glucose (eg lucozade/glucogel) if conscious, if unconscious then IM glucagon or IV 20% dextrose
  • review meds/treat cause
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15
Q

Diabetic foot

A

Due to

  • reduced recognition of damage - visual impairment, sensory neuropathy
  • reduced protective mechanisms - dry skin, PAD
  • abnormal plantar pressurs - bunions, Charcot’s deformity

Ix

  • FBC (infection)
  • blood glucose
  • Xray of foot
  • ABPI

Mx

  • dressings for moist environment
  • podiatrist
  • address nutrition
  • abx
  • surgery to debride/amputate if needed
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16
Q

Hyponatraemia

A

<135mmol/L
- nausea, headache, confusion, seizures, lethargy, muscle weakness/cramps
+ maybe signs of volume expansion or depletion

Risk factors
- old age, hospitalisation, SSRIs, thiazides, comorbidities, ecstasy

Diagnosis

  1. Exclude pseudohyponatraemia (if lipaemia/hyperproteinaemia) and compensatory hypoNa (if hyperglycaemia)
  2. Determine if volume expanded, depleted or euvolaemic
  3. Measure urine sodium
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17
Q

Volume depleted hyponatraemia

A

If urinary Na >30
= renal loss
- diuretics (esp thiazides)
- Addison’s disease (low aldosterone)

If urinary Na<30
= extra-renal loss
- vomiting / diarrhoea (when severe, RAAS can’t cope so ADH system is switched on)

Treat both with normal saline

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18
Q

Euvolaemic hyponatraemia

A

Urinary Na >30

  • SIADH (syndrome of inappropriate ADH) - diagnosis of exclusion only
  • hypothyroidism

Fluid restrict

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19
Q

Volume expanded hyponatraemia

A

Urinary Na <30 + oedema

  • nephrotic (loss of albumin, ADH kicks in)
  • cirrhosis (less production of albumin, ADH kicks in)
  • heart failure (fluid into interstitium, dropped intravascular volume, ADH kicks in)

Fluid restrict

20
Q

Hypocalcaemia

A

CATS symptoms
- convulsions, arrhythmias, tetany, spasms and stridor
(Chvostek’s and Trousseau’s signs, lethargy, depression, psychosis, paraesthesia, long QT / arrhythmias, soft tissue disorder)

Caused by

  • artefact! (low albumin / unsuitable sample if U+Es not taken before FBC)
  • decreased intake/absorption - vit D deficiency
  • decreased flux of calcium from bone - hypoPTH (surgical removal, autoimmune, congenital Di George syndrome, Mg deficiency)
  • increased flux of calcium to bone - hungry bone syndrome (hyperPTH then removed)
  • acute pancreatitis
  • hyperventilation (resp alkalosis -> less H+ bound to albumin -> more free Ca binds -> hypocalcaemia)

Treat with oral vit D and IV calcium gluconate

21
Q

Hypercalcaemia

A

Bone pain
Stones (calculi, polyuria)
Groans (abdo pain, constipation, nausea)
Psychic moans (depression, fatigue, confusion)

Causes (hyperPTH or malignancy almost always!)

  • artefact - dehydration, prolonged tourniquet use
  • increased intake/absorption - excess vit D, sarcoidosis
  • increased bone resorption - primary hyperPTH, malignancy, immobilisation, thyrotoxicosis
  • increased renal absorption - thiazides
  • familial hypocalciuric hypercalcaemia

Most in women in 50s, cancer, fhx

Ix

  • ECG - short QT
  • serum calcium, PTH, vit D, LFTs

Mx

  • rehydration
  • bisphosphonates
  • steroids if cancer
22
Q

Acute adrenal crisis

A

= Addisonian crisis, medical emergency from acute lack of adrenal hormones including cortisol and aldosterone

Presentation

  • sudden penetrating pain in legs, lower back, abdomen
  • confusion, lethargy, psychosis, convulsions
  • fever
  • hyperK+, hypoNa+
  • hypotension, syncope
  • severe vomiting and dehydration

Causes

  • usually in Addison’s disease, with rapid deterioration when stressed (trauma, illness, dehydration)
  • congenital adrenal hyperplasia / pituitary syndromes rarely also

Ix

  • FBC, CRP, electrolytes
  • cortisol
  • ACTH stimulation test

Mx

  • hydrocortisone
  • fluid support
23
Q

Thyroid eye disease

A

= Graves’ ophthalmopathy
- autoimmune inflammatory disorder of the muscles in the orbit - see upper eyelid retraction, lid lag, exophthalmos, erythema, diplopia, temporary loss of colour vision, Stellwag’s sign (incomplete blinking)

Usually from Graves’ disease, rarely in Hashimoto’s/euthyroid
- more in older age, smokers, diabetes, hyperthyroid, pretibial myxoedema

Ix

  • clinical examination
  • MRI head (oedema of orbital muscles)

Mx

  • conservative - stop smoking, artificial tears
  • medical - glucocorticoids, infliximab
  • surgical - decompression surgery
24
Q

Thyroid cancer

A
  • palpable thyroid nodule, F>M

Types (most common, best prognosis)
Papillary - age 20-40, lymph spread, good prognosis
Follicular - age 40-50, haem spread
Anaplastic - age 60+, direct agressive spread, poor prognosis
Medullary - age 60+, variable prognosis

Ix

  • TSH almost always normal
  • USS with fine needle biopsy

Mx

  • papillary/follicular - surgery, radioactive iodine ablation, levothyroxine replacement lifelong
  • anaplastic - surgery, palliative chemo, levothyroxine
25
Hypoparathyroidism
Low PTH -> low calcium, high phosphate - asymptomatic, or if severe then signs of hypocalcaemia (muscle twitches, paraesthesia, Chvostek's sign) Causes - very common after neck (thyroid) surgery - congenital (DiGeorge syndrome) - due to low Mg - autoimmune destruction of PTH Ix - ECG - prolonged QT - low calcium - high phosphate Mx - acute - IV calcium, parenteral Mg - chronic - oral calcium, active vit D, human recombinant PTH 2nd line
26
Primary aldosteronism
= Conn's syndrome, most common treatable cause of hypertension (5% of all) - HTN + nocturia, polyuria (from excess aldosteronism -> water retention) Ix - aldosterone/renin ratio raised - hypokalaemia Mx - if unilateral form - remove one adrenal gland surgically - if bilateral (most) - medical aldosterone antagonist
27
Phaeochromocytoma
= tumour from catecholamine-producing chromaffin cells of the adrenal medulla (rare cause of HTN) - 90% in adrenal gland, but can be extra-adrenal in head/neck - genetic/syndrome predispositions Presentation - adrenaline! - headaches - diaphoresis (sweating) - palpitations - paroxysmal HTN - impaired glucose tolerance/DM Ix - 24hr urine for catecolamines - plasma catecholamines - genetic testing - CT abdo pelvis - FDG-PET scan Mx - medical - alpha blocker eg doxazosin, then B blocker eg propanolol 2nd line - surgical - adrenalectomy ± chemo
28
Hypopituitarism
Symptoms depend on which hormones deficient - GH -> failure to thrive/shortness in children - FSH/LH -> infertility/oligomenorrhoea - ACTH -> adrenal insufficiency inc hypoglycaemia - TSH -> hypothyroid Causes - neoplastic (benign adenoma compresses normal tissue) - vascular (pituitary apoplexy / Sheehan's syndrome (blood loss in childbirth) / SAH) - infiltrative (haemochromotosis, sarcoidosis, TB) - radiotherapy - trauma - empty sella syndrome - congenital / infective (rare) Ix - serum electrolytes - 8am hormones - cortisol, ACTH, testosterone, oestrogen, LH, FSH, IGF-1 - MRI pituitary Mx - replace hormone deficiency - cortisol (ACTH), levothyroxine (TSH), oestrogen/progesterone/testosterone (GnRH)
29
Pituitary tumours
- almost always adenomas (functioning or non) Symptoms according to which hormone in excess (most-least common) - GH -> acromegaly - non-functioning - FSH/LH -> infertility/oligomenorrhoea - ACTH -> Cushing's - TSH -> hyperthyroid Ix - MRI pituitary - serum electrolytes - 8am hormone testing Mx - conservative - medical - radiotherapy, hormone suppressor therapy - surgical - trans-sphenoidal surgical resection
30
Acromegaly
- caused by GH secreting pituitary adenoma - chronic progressive multisystem disease -> morbidity and mortality Presentation - coarsened facial features, soft-tissue hypertrophy, organomegaly - carpal tunnel, joint pain/dysfunction - snoring/sleep apnoea - altered sexual function - fatigue - HTN - impaired glucose tolerance/DM Ix - serum IGF-1 - oral glucose tolerance test - random serum GH - MRI pituitary Mx - medical - somatostatin analogue, GH receptor antagonist surgical - trans-sphenoidal resection ± adjunct radiotherapy
31
Diabetes insipidus
= defiency to ADH (vasopressin) - central DI - defective release from posterior pituitary - nephrogenic DI - ADH not detected properly by collecting duct Presentation - polyuria - polydipsia - nocturia - hypernatraemia - hyperreflexia, spasticity, lethargy, delirium, seizures, coma - volume depletion - dry, tachycardia, hypotension Ix - low urine osmolality - high serum osmolality, high sodium, high calcium, low potassium - no glucose in urine dip - high serum urea Mx - central - desmopressin - nephrogenic - stay hydrated - acute hypernatraemia - IV fluids
32
Hypogonadism
= diminished function of testes or ovaries - decreased libido, ED, gynaecomastia, infertility, delayed puberty Primary = hypogonadotrophic hypogonadism = failure of gonads, so rise in GnRH/LH/FSH - Kleinfelter's syndrome XXY - cryptorchidism - mumps - drugs (opioids, glucocorticoids) - testicular tumour Secondary = failure in hypothalamus, so low GnRH/LH/FSH - pituitary deficiency/tumours - Kallmann syndrome - hyperprolactinaemia - empty sella syndrome - infiltrative disease - radiation - drugs Give testosterone / oestrogen/progesterone therapy
33
Insulin
- twice daily mixed insulins - basal bolus regimen (long acting + shorts, useful in T1 to adjust according to meals) - once daily basal (T2DM only) - must be adjusted according to exercise, fingerprick glucose, calorie intake, carbohydrates - in illness, don't stop insulin, maintain calorie intake and check BMs (ketones!) more ``` Short acting - soluble, unmodified - actrapid, humulog, novorapid Intermediate acting - insulatard, humulin I Long acting (for bedtime) - glargine Pre-mixed eg Humulin M3 (30% soluble) ``` Side effects: hypoglycaemia, but maybe also hypokalaemia, resistance, local lipodystrophy
34
Sulphonylureas
eg gliclazide, increases amount of insulin secreted by B cells, so useful in T2DM - if tried lifestyle modification for 12 weeks and persistent symptoms SEs - hypoglycaemia - hunger - weight gain NOT in impaired liver/kidney function
35
T2DM management
1. lifestyle modification (12 weeks) 2. monotherapy - standard release metformin, or if not tolerated one of sulphonylurea, gliptin, pioglitazone, SGLT2i 3. dual therapy 4. triple therapy, or insulin-based therapy
36
Biguanides
eg metformin, increases body sensitivity to insulin (doesn't affect insulin release) - 1st line if tried lifestyle modification for 12 weeks and persistent symptoms SEs - diarrhoea - dyspepsia - NOT hypoglycaemia - lactic acidosis, so not used if eGFR<30
37
Thiazolidine
eg pioglitazone, increases sensitivity to insulin (similar effects to metformin) ``` SEs - increased fracture risk - fluid retention/oedema - weight gain - hypoglycaemia - LFT derangement NOT in CCF, liver disease, or OP ```
38
DPP4 inhibitors
= gliptin eg linagliptin Cause insulin release by increasing incretin GLP1 antagonists eg exanitide similar
39
SGLT2i
= selective sodium-glucose co-transporter 2 inhibitor, eg dapaglifozin Blocks reabsorption of glucose in kidneys, so promotes excretion in urine - so SEs of UTI/thrush risk, dehydration - never in AKI
40
Levothyroxine
= artificial T4 thyroxine Used in hypothyroidism SEs (as in hyperthyroid) - weight loss - heat intolerance - diarrhoea - tremor - tachycardia - palpitations Not if recent MI!
41
Anti-thyroid drugs
eg carbimazole, propylthiouracil, iodine-131 - work by inhibiting thyroid peroxidase (which oxidises iodide) Carbimazole - takes 4 weeks for effect - SEs agranulocytosis so stop and urgent blood test for low neutrophils if see any signs of infection Radioiodine - will usually lead to hypothyroid after treatment, not in pregnancy or lactation (no cancer risk)
42
Bisphosphonates
eg alendronate, zolendronate - inhibits osteoclasts to increases bone marrow density - for OP, bone breakdown after cancer, Paget's disease, OI Alendronate - oral, so GI side effects (take on empty stomach, stay upright for 1hr after) Zolendronate - IV With long term use. risk atypical hip fractures or osteonecrosis of the jaw
43
Vitamin D and calcium supplementation
eg calcitriol (activated vitamin D) - to boost calcium and vitamin D, so to protect bone and prevent hypocalcaemia - in OP, rickets, hypocalc, OM, CKD SEs - hypercalc (bones, stones, groans, moans)
44
Corticosteroids
eg prednisolone, hydrocortisone - long term (>3weeks) must NOT be stopped suddenly as risk Addisonian crisis - some conditions may be worsened (HTN, OP, diabetes) - caution in pregnancy - avoid NSAIDs (ulcers)
45
Dexamethasone suppression tests
Low dose (1mg at night) - > low cortisol = normal - > high/normal cortisol = cushing's syndrome then go on to... High dose (8mg at night) - > low cortisol = Cushing's disease (pituitary) - > high cortisol, low ACTH = adrenal cushing's - > high cortisol, high ACTH = ectopic ACTH