Endocrinology Flashcards
1
Q
Differentials for gynaecomastia
A
- Normal in puberty
- Syndromes with androgen deficiency = Kallman’s, Klinefelter’s
- Testicular failure = mumps
- Liver disease
- Testicular cancer
- Ectopic tumour secretion
- Hyperthyroidism
- Medications
2
Q
Medications causing gynaecomastia
A
o Spironolactone
o Cimetidine
o Digoxin
o Cannabis
o Finasteride
o GnRH agonists: goserelin, buserelin
o Oestrogens, anabolic steroids
3
Q
Causes of hypokalaemia with hypertension
A
- Cushing’s
- Conns
- Liddle’s syndrome
- 11-beta hydroxylase deficiency
4
Q
Causes of hypokalaemia WITHOUT hypertension
A
- Diuretics
- GI loss
- Renal tubular acidosis
- Bartter’s syndrome
- Gitelman syndrome
5
Q
What is acromegaly?
A
Increase secretion of growth hormone from pituitary tumour
6
Q
Causes of acromegaly
A
- MEN-1 (multiple endocrine neoplasia-1)
- Pituitary adenoma
- Hyperplasia (rare)
- Secondary to cancer (lung, pancreatic) = secretes ectopic GHRH/GH
7
Q
Presentation of acromegaly
A
- Headaches (very common)
- Increased size of hands and feet
- Increase weight
- Excessive sweating
- Visual deterioration
- Fatigue
- Deep voice
- Decreased libido
- Arthralgia and backache
- Acroparaesthesia = pain, tingling and numbness of extremities
- Maxillofacial changes
- Hypogonadal symptoms = Amenorrhea
- Bitemporal hemianopia
- Skin darkening
- Coarsening face with large tongue, nose, protruding jaw
- Prognathism
- Big supraorbital ridge
- Interdental separation
- Goitre
- Curly hair
- Oily large pored skin
- Scalp folds
- Carpal tunnel syndrome (50%)
8
Q
1st line investigation for acromegaly
A
Insulin-like Growth factor 1 raised
9
Q
Gold standard investigation for acromegaly
A
Oral glucose tolerance test = high glucose normally suppressed by GH
10
Q
Management of acromegaly
A
- 1st line = Trans-sphenoidal removal of pituitary tumour
- Surgical removal of ectopic secreting cancers
- SC Pegvisomant daily = GH antagonist
- Somatostatin analogues (ocreotide) = inhibits GH release
- Dopamine agonist (bromocriptine) = weakly control IGF-1
11
Q
Complications of acromegaly
A
- Impaired glucose tolerance (40%)
- Diabetes mellitus (15%)
- Sleep apnoea = excess soft tissue in larynx
- Hypertension, left ventricular hypertrophy, cardiomyopathy, arrhythmias, ischaemic heart disease, stroke
- Colon cancer
- Arthritis
- Cerebrovascular events and headache
- Enlargement of joints and soft tissues
- Decreased life expectancy
12
Q
What is diabetes insipidus?
A
Reduced ADH secretion from posterior pituitary or impaired response to ADH
13
Q
Cranial causes of diabetes insipidus
A
o Brain Tumour = metastases, posterior pituitary tumour
o Head Trauma
o Brain malformations
o Brain Infections = TB, encephalitis, meningitis
o Brain surgery or radiotherapy
o Infiltrative disease = sarcoidosis
o Vascular = aneurysm, infarction, sickle cell
o Inflammatory = neurosarcoidosis, Guillain Barre, granuloma
14
Q
Nephrogenic causes of diabetes insipidus
A
o Drugs = lithium chloride, glibenclamide
o Familial = mutation AVPR2 gene on X chromosome
o Intrinsic kidney disease
o Electrolyte disturbance = Hypokalaemia and Hypercalcaemia
15
Q
Presentation of diabetes insipidus
A
- Polyuria
- Polydipsia
- Dehydration
- Postural hypotension
- Hypernatraemia = lethargy, weakness, irritability, confusion, coma and fits
16
Q
Investigation for diabetes insipidus
A
- Water deprivation test
o Serum and urine osmolality, urine volume and body weight are measured hourly for up to 8 hours during fasting and without fluids
o Normal response = serum osmolality remains within normal range while urine rises
o DI = serum osmolality rises without adequate conc of urine
o Then desmopressin administered and urine osmolality measured 8 hours later
o Cranial DI (kidneys still respond to ADH) = urine osmolality high
o Nephrogenic DI (can’t respond to ADH) = low urine osmolality
17
Q
Management of diabetes insipidus
A
- Treat underlying cause
- Desmopressin (synthetic ADH) = cranial DI
- Nephrogenic DI
o Thiazide diuretics = oral Bendroflumethiazide
o NSAIDs
18
Q
What is SIADH?
A
Continued secretion of ADH despite plasma being very dilute
19
Q
Causes of SIADH
A
- Post-operative from major surgery
- Infection = atypical pneumonia and lung abscesses, TB
- Medications = thiazide diuretics, carbamazepine, vincristine, cyclophosphamide, antipsychotics, SSRIs, NSAIDs
- Malignancy = small cell lung cancer, pancreas, prostate
- Neurological = Meningitis/encephalitis, SAH, SDH, stroke, head injury
- Pulmonary lesions = pneumonia, TB, CF, asthma
- Alcohol withdrawal
20
Q
Presentation of SIADH
A
- Headache
- Fatigue
- Muscle aches and cramps
- Confusion
- Seizures and reduced consciousness = severe hyponatraemia
- Anorexia and nausea
- Irritability
- Unstable gait/falls
21
Q
Investigations for SIADH
A
- Dilutional hyponatraemia = excessive water retention
- Euvolaemia = normal blood vol
- High urine Na+ > 30 mmol/L
- Negative short synacthen test = exclude adrenal insufficiency
- 1-2L or 0.9% Saline = sodium depletion will respond but SIADH won’t
22
Q
Management of SIADH
A
- Treat underlying cause
- Fluid restriction = 500ml-1L
- ADH receptor blockers (tolvaptan) = close monitoring
- Demeclocycline = tetracycline Abx inhibits ADH
- Hypertonic saline
- Salt and loop diuretic = oral furosemide
23
Q
Complication of SIADH
A
Central pontine myelinolysis = brain swelling
24
Q
What is Conn’s syndrome?
A
Primary hyperaldosteronism from adrenal adenoma
25
Causes of primary hyperaldosteronism
- Adrenal adenoma (Conn’s syndrome)
- Bilateral adrenocortical hyperplasia
- Familial hyperaldosteronism type 1 and 2
- Adrenal carcinoma
26
Presentation of primary hyperaldosteronism
- Often asymptomatic
- Weakness/cramps
- Paraesthesia, polyuria and polydipsia
- Hypertension = severe increase in blood volume
- Hypokalaemia
27
Investigations for primary hyperaldosteronism
- Plasma aldosterone: renin ratio
o High aldosterone and low renin = primary hyperaldosteronism
o High aldosterone and high renin = secondary hyperaldosteronism
- Increased plasma aldosterone levels not suppressed with 0.9% saline infusion or fludrocortisone administration = diagnostic
- ABG = alkalosis
- Hypokalaemic ECG = Flat t waves, ST depression, long QT
- CT or MRI adrenals to differentiate adenomas from hyperplasia
- Renal doppler ultrasound = renal artery stenosis or obstruction
28
Management of primary hyperaldosteronism
- Aldosterone antagonists = Oral spironolactone
- Laparoscopic adrenalectomy
- Percutaneous renal artery angioplasty = renal artery stenosis
29
Complications of primary hyperaldosteronism
Renal, cardiac and retinal damage
30
What is addison's disease?
Autoimmune damage to adrenal glands causing reduction in secretion of cortisol and aldosterone (Primary adrenal insufficiency)
31
Causes of primary adrenal insufficiency
- Autoimmune adrenalitis
- TB
- Adrenal metastases
- Long term steroid use
- Adrenal haemorrhage/infarction = meningococcal septicaemia
32
Presentation of Addison's disease
- Toned = lean build, anorexia, weight loss
- Tanned Pigmentation of skin (increased ACTH) cross reacts with melanin receptors
- Tired = lethargy
- Tearful = depression, low mood and self esteem
- Nausea and vomiting
- Diarrhoea, constipation and abdominal pain
- Impotence/amenorrhea
- Dizzy, syncope
- Headache
- Cramps
- Reduced libido
- Vitiligo = white patches and loss of body hair due to loss of adrenal androgens
- Dehydration
33
Investigations of primary adrenal insufficiency
- Short synACTHen test (ACTH stimulation)
o Measure plasma cortisol before and 30 mins after IM tetracosactide
o Addison’s excluded if 30 mins cortisol >550nmo/L Hyponatraemia and Hyperkalaemia
- Adrenal autoantibodies adrenal cortex antibodies and 21-hyroxylase antibodies
34
Electrolyte abnormalities in Addison's disease
hyperkalaemia, hyponatraemia, hypoglycaemia, metabolic acidosis
35
Management of primary adrenal insufficiency
- Oral hydrocortisone = glucocorticoid replacement
- Oral fludrocortisone = mineralocorticoid replacement
- Steroid card and emergency ID tag
- Hydrocortisone dose doubled during acute illness
36
Complications of primary adrenal insuffiency
- Critical deterioration = shock, raised temp, coma
- Adrenal crisis
o Nausea, vomiting, abdominal pain, muscle cramps and confusion
o IV hydrocortisone immediately
- CVD risk increased
- Osteoporosis
37
Causes of secondary adrenal insufficiency
- Loss or damage to pituitary gland = hypopituitarism
- Surgery to remove pituitary tumour
- Infection
- Loss of blood flow
- Radiotherapy
- Long term steroid therapy
- Hypothalamic-pituitary disease
38
Causes of hypercalcaemia
- Long term immobility
- Hyperparathyroidism (primary, secondary, tertiary)
- Malignant hyperparathyroidism
- Excess Ca2+ intake
- Drugs = thiazide diuretics, vit D analogies, lithium administration
39
Presentation of hypercalcaemia
- Can be asymptomatic if mild
- Stones = renal colic, biliary stones
- Bones = Pain, fractures, osteomalacia/osteoporosis
- Groans = abdo pain, N+V
- Psychic moans = Depression, anxiety, cognitive dysfunction, insomnia and coma
- Thrones: Polyuria and polydipsia, Constipation
- Other: Weakness, fatigue, muscle symptoms, Anorexia and weight loss
- Hypertension
40
Investigations for hypercalcaemia
- High serum Ca2+, High 24 hr urinary Ca2+, raised ALP (malignancy), raised PTH
- Low renal function = 2nd/3rd
- AXR renal calculi or nephrocalcinosis
- Skull XR pepper-pot
- Hand XR subperiosteal erosions in middle/terminal phalanges
- Parathyroid ultrasound insensitive for small tumours
- Radioisotope scanning = 90% sensitive for detecting adenoma
- High res CT/MRI malignancies around body
- DEXA bone density scan
41
Management of acute severe hypercalcaemia
o Rehydrate with IV 0.9% saline fluids = prevent stones
o Bisphosphonates after rehydration (IV pamidronate)
o Oral prednisolone = myeloma, sarcoidosis and vit D excess
42
Management of primary hyperparathyroidism
o Parathyroid adenoma/hyperplasia = surgical removal
o Calcimimetic = increases sensitivity of parathyroid cells to Ca2+
o Avoid thiazide diuretics, high Ca2+ and vit D intake
43
Causes of hypocalcaemia
- CKD
- Severe vit D deficiency (Osteomalacia)
- Drugs = calcitonin, bisphosphonates
- Acute pancreatitis
- Massive blood transfusion
- Rhabdomyolysis
- Magnesium deficiency
44
What is primary hypoparathyroidism
Low PTH due to parathyroid gland failure
o Ca2+ is low and phosphate high
45
Presentation of hypocalcaemia
- Parathesiae (numbness and tingling) around mouth and extremities
- Cramps, tetany
- Diarrhoea
- Anxious, irritable, irrational
- Wheeze = muscle tone increases in smooth muscle
- Orientation impaired and confusion
- Dermatitis ± Impetigo herpetiformis
- Chvostek’s sign = Tapping over facial nerve causes twitching of ipsilateral facial muscles
- Trousseau’s sign = Carpopedal spasm induced by inflammation of sphygmomanometer cuff to level above systolic pressure
- Papilloedema, Cataract
- Cardiomyopathy
46
Investigations of hypocalcaemia
- Bloods = Low serum Ca2+, eGFR, creatinine, urine, low Mg, low vit D
- PTH absent or low in hypoparathyroidism but high in other causes of hypocalcaemia
- Parathyroid antibodies = present in idiopathic hypoparathyroidism
- X-rays of metacarpals = short 4th metacarpal in pseudohypoparathyroidism
- ECG prolonged QT interval
47
Management of hypocalcaemia
- Give IV calcium gluconate 10ml of 10% every 10 mins over 30 mins with ECG monitoring
- Vit D deficiency = Oral colecalciferol/adcal
- Hypoparathyroidism = Calcium supplements and calcitriol (active vit D)
48
Difference between Cushing's disease and Cushing's syndrome
- Syndrome = Too much cortisol
- Disease = pituitary adenoma secretes excess ACTH leading to increased cortisol
49
Risk factors for Cushings
Depression
Obesity
Pregnancy
50
Causes of Cushings
- Oral steroids = glucocorticoid therapy (most common)
- Pituitary adenoma (Cushing’s disease)
- Adrenal adenoma
- Paraneoplastic Cushing’s = small cell lung cancer
- Alcohol pseudo-Cushing’s syndrome
51
Presentation of Cushings
- Central obesity (trunk, abdomen and neck) = weight gain
- Ruddy and swollen with moon face
- Bruising
- Thin skin
- Gonadal dysfunction (irregular periods and erectile dysfunction)
- Acne
- Failure for children to grow tall despite excess weight
- Recurrent non healing ulcers
- Hirsutism Excess hair in chin and moustache area
- Lethargy
- Striae = Purply stretch marks on abdomen, breasts and thighs
- Buffalo hump = fat pad on upper back
- Proximal limb muscle wasting + weakness
- Malaise, depression, psychosis, insomnia
52
Investigation for Cushings
- Overnight dexamethasone suppression test
Low dose
o If low cortisol then normal
- if high/normal then Cushings
High dose
If low then Cushings disease
If high/normal then check ACTH
ACTH low = adrenal cushings
ACTH high = ectopic ACTH
53
What is T1DM?
Insulin deficiency from autoimmune destruction of pancreatic insulin-secreting Beta cells in islets of Langerhans
54
Risk factors for T1DM
- Family history (HLA DR3/4)
- Other autoimmune diseases = autoimmune thyroid, coeliac disease, Addison’s disease, pernicious anaemia
- Environment = Dietary constituents, Enteroviruses, Vit D deficiency
55
Presentation of T1DM
- Thirsty (polydipsia)
- Polyuria and nocturia
- Weight loss/lean
- Fatigue
- Glycosuria
- Breath smelling of ketones
- Persistent hyperglycaemia = Despite diet and medications
- Ketonuria
56
Investigations for T1DM
- Random plasma glucose >11.1mmol/L
- Fasting plasma glucose >7mmol/L = One abnormal value is diagnostic in symptomatic individuals and 2 in asymptomatic individuals
C-peptide levels low
Metabolic acidosis
57
Antibodies in T1DM
o Anti-GAD
o Islet cell antibodies
o Insulin autoantibodies
o Insulinoma-associated 2 autoantibodies
58
Management of T1DM
Lifelong insulin therapy
59
Advice for T1DM
- Must inform DVLA = Advise not to drive if severe hypoglycaemic spells
- Good control to educate to self-adjust doses
- Can phone for support 24/7 nurse
- Can modify diet wisely and avoid binge drinking
- Abort hypoglycaemia with sugary drinks
- Finger pricking glucose
o Before meal = inform long-acting insulin doses
o After meal = inform short-acting insulin doses
60
Complications of T1DM
- Diabetic Ketoacidosis
- Insulin treatment
o Hypoglycaemia
o Injection site = lipohypertrophy
o Insulin resistance
o Weight gain
- Coronary artery disease
- Peripheral neuropathy
o Tx: amitriptyline, duloxetine, gabapentin, pregabalin
- Gastrointestinal autonomic neuropathy
o Gastroparesis erratic blood glucose control, bloating, vomiting
o Chronic diarrhoea
o GORD
- Retinopathy
61
What is T2DM
Decreased insulin secretion with/out increased insulin resistance
62
Organic causes of T2DM
- Combination of insulin resistance and less severe insulin deficiency
- Drugs = steroids, anti-HIV drugs, new antipsychotics, thiazides
- Pancreatitis, pancreatic surgery, trauma, pancreatic cancer
- Cushing’s disease, acromegaly, hyperthyroidism
- Pregnancy
- Congenital lipodystrophy, glycogen storage diseases
63
Investigations of T2DM
- Random plasma glucose >11.1mmol/L, Fasting plasma glucose >7mmol/L
- HbA1c >48mmol/mol
64
Pharmacological management of T2DM
Oral metformin
Add SGLT-2 inhibitors
Add sulfonyluriea (gliclazide)
Add pioglitazone
Add sitagliptin
Add insulin therapy
65
Side effects of metformin
diarrhoea, abdo pain, lactic acidosis
66
Side effects of sulfonylurea (gliclazide)
weight gain, hypoglycaemia, increased CVD/MI risk, liver dysfunction
67
Side effects of pioglitazone
weight gain, fluid retention, anaemia, heart failure, liver dysfunction, fractures
Contraindicated in heart failure
68
Side effects of SGLT-2 inhibitors (empahlifozin)
urinary and genital infection, Fournier’s gangrene, normoglycaemic ketoacidosis, increase risk of lower limb amputation
69
Positive effects of SGLT-2 inhibitors
Improve outcomes for patients with CVD
Weight loss
70
Complications of T2DM
- Atherosclerosis = stroke, IHD, MI and peripheral vascular disease (gangrene)
- Diabetic Retinopathy
- Diabetic Polyneuropathy = Diabetic foot ulceration
- Erectile dysfunction
- CKD (10%) = Diabetic nephropathy
- Infections (6%)
71
Causes of hyperthyroidism
- Grave’s disease
- Toxic multi nodular goitre
- Toxic adenoma (benign)
- Ectopic thyroid tissue
- Drug-induced hyperthyroidism = amiodarone, iodine, lithium
- Thyroiditis (De Quervain’s)
- Hashimoto’s, postpartum
72
Presentation of hyperthyroidism
- Palpitations, tachycardia
- Heat intolerance = sweating
- Anxiety
- Diarrhoea (Frequent loose stools)
- Weight loss and increased appetite
- Oligomenorrhea (infrequent periods) and infertility
- Irritability/ behavioural change
- Sexual dysfunction
- Goitre
- Hyperkinesis = muscle spasm
- Proximal myopathy and muscle wasting
- Lymphadenopathy and splenomegaly
- Hands = palmar erythema, warm moist skin and fine tremor
- Lid lag and stare
73
Investigations for hyperthyroidism
- TFTs serum TSH low, T4/T3 high
- Raised ESR and CRP = thyroiditis
- Thyroid peroxidase (TPO) and thyroglobulin antibodies = 80% of Graves’ but all normal hyperthyroidism
- Ultrasound of thyroid = differentiate Graves’ from toxic adenoma
- TSH receptor stimulating antibodies = Graves’ specific
74
Management of hyperthyroidism
- Anti-thyroid drugs
1. Oral Carbimazole
2. Propylthiouracil
- Radioactive iodine = destroys portion of thyroid cells
o Treatment of choice to toxic multinodular goitre
- BB (propranolol) = rapid control of symptoms
- Surgery (thyroidectomy) = Large goitre, poor response to drugs and have drug side-effects
- Thyroid pain aspirin/NSAIDs
75
Complications of hyperthyroidism
Thyroid crises/storm
76
Presentation of thyroid storm
fever > 38.5ºC
tachycardia
confusion and agitation
nausea and vomiting
hypertension
heart failure
abnormal liver function test - jaundice may be seen clinically
77
Management of thyroid storm
symptomatic treatment e.g. paracetamol
treatment of underlying precipitating event
beta-blockers: typically IV propranolol
anti-thyroid drugs: e.g. methimazole or propylthiouracil
Lugol's iodine
dexamethasone - e.g. 4mg IV qds - blocks the conversion of T4 to T3
78
What is Grave's disease?
Autoimmune condition where TSH receptor antibodies cause primary hyperthyroidism
79
What features are specific to Grave's disease
Grave's ophthalmopathy = protruding eye and proptosis, eye discomfort, corneal ulceration, paralysis of eye muscles
Grave's dermopathy = pretibial myxoedema
TSH receptor stimulating antibodies
80
What are the different types of thyroid cancers?
Papillary = young, well differentiated, good prognosis
Follicular = middle age, well differentaited, good prognosis
Anaplastic = aggressive, very undifferentiated, poor prognosis
Lymphoma
Medullary cell
81
Presentation of thyroid cancers
- Dysphagia
- Hoarse voice = tumour compression on surrounding structures (oesophagus and laryngeal nerve)
- Thyroid nodules (90%)
- Cervical lymphadenopathy or with lung, cerebral, hepatic or bone metastases
- Thyroid gland = large, hard, irregular
82
Investigations for thyroid cancers
- Fine needle aspiration cytology biopsy = benign or malignant nodules
- Ultrasound of thyroid = Differentiate between benign or malignant
Blood test (TFT)
o Check if hyperthyroid or hypothyroid = treated before carcinoma surgery
o T3, T4, TSH, thyroid autoantibodies
- CXR = Tracheal goitres, mets
83
Management of thyroid cancers
- Thyroidectomy
- Radioactive Iodine Locally irradiate and destroy cancer with little radiation damage to other surrounding structures
- Levothyroxine (T4) Keep TSH reduced (growth factor for cancer)
- Chemotherapy Reduce risk of spread and treats micro-metastases that have been undetected
84
Causes of hypothyroidism
- Hashimoto’s thyroiditis (developed world)
- Iodine deficiency (developing world)
- Post-thyroidectomy/ radioiodine/ anti thyroid drugs
- Post-partum thyroiditis
- Drug induced = Carbimazole, lithium, amiodarone, interferon Secondary hypothyroidism (reduced TSH from anterior pituitary)
- Hypopituitarism = tumours, infection, vascular, radiation
- Other autoimmune disease
85
Presentation of hypothyroidism
- Weight gain
- Hoarse voice
- Goitre
- Constipation
- Menorrhagia
- Myalgia, weakness
- Low mood, dementia
- Myxoedma
- Bradycardia
- Reflexes relax slowly
- Ataxia (cerebellar)
- Dry, thin hair/skin
- Yawning/drowsy/coma
- Cold hands (temp drop)
- Ascites (Fluid retention = oedema, pleural effusions)
- Round puffy face
- Defeated demeanour
- Immobile (ileus)
- Congestive cardiac failure
86
Investigations for hypothyroidism
- Thyroid function tests
o Serum TSH high (primary hypothyroidism)
o Serum TSH low (secondary hypothyroidism)
o Serum free T4/T3 low (both)
- TPO antibodies Hashimoto’s
- Raised serum aspartate transferase levels from muscle and/or liver
- Increase serum creatinine kinase levels (myopathy)
- Hypercholesterolaemia
- Hyponatraemia = increase in ADH and impaired free water clearance
87
Management of hypothyroidism
Lifelong oral levothyroxine
88
Complications of hypothyroidism
- Myxoedema coma
o Severe hypothyroidism = rarely present with confusion and coma
o Hypothermia, cardiac failure, hypoventilation, hypoglycaemia and hyponatraemia
o Medical emergency IV/oral T3 + glucose infusion as well as gradual rewarming
- Dyslipidemia
- Metabolic syndrome
- CHD and stroke
- HF
- Neurological and cognitive impairments
- MALT lymphoma (Hashimoto’s)
