Endocrine Flashcards
1
Q
T1DM Definition
A
Metabolic disorder characterised by hyperglycaemia
2
Q
T1DM Epidemiology
A
Young (<30yrs), lean, North Europe (can occur at any age)
3
Q
T1DM Aetiology
A
Autoimmune = beta cells destroyed - not make insulin
4
Q
T1DM RFs
A
FHx + PHx autoimmune disease (HLA-DR3/4)
5
Q
T1DM Path
A
Abs against insulin, glutamic acid decarboxylase, islet auto-antigen-2.
Beta cell destruction = subclinical for months - years.
80-90% destroyed = hyperglycaemia.
Patients cannot use glucose in peripheral muscle/adipose = stimulates glucagon secretion = gluconeogenesis, glycogenolysis and ketogenesis in liver = hyperglycaemia + anion gap metabolic acidosis
6
Q
Hyperglycaemia path
A
Hyperglycaemia = inflammation + oxidative stress = endothelial dysfunction by NO = LDLP enters vessel wall = slow inflammatory response = atherosclerosis.
7
Q
T1DM Signs
A
Ketoacidosis, low BMI, young age, weight loss, glycosuria
8
Q
T1DM Sx
A
Thirst (osmotic activation of hypothalamus), dry mouth, fatigue, hunger, weight loss, nausea/vomiting, skin infections, vaginal candidiasis, blurred vision
9
Q
T1DM Investigations - 1st
A
Random glucose tolerance test (GP) >11.1mmol/L
Fasting plasma glucose, 2-hr plasma glucose, plasma, urine ketones. Low C peptide
10
Q
T1DM Investigations - Gold
A
Glycated haemoglobin A1C (HbA1c) = av. blood sugar for past 2-3 mths = measures % glucose attached to Hb >48mmol/mol (6.5%) = diabetes
11
Q
T1DM Treatment
A
1st: Basal-bolus insulin, pre-insulin correction dose, amylin analogue (pramlintide)
2nd: fixed insulin dose - Side effects = hypoglycaemia, weight gain, lipodystrophy
12
Q
T1DM Complications
A
Microvascular - retinopathy, nephropathy, peripheral neuropathy
Macrovascular - CAD, cerebrovascular disease, PAD
13
Q
T1DM Prognosis
A
Untreated = fatal (diabetic ketoacidosis). Poorly controlled = RF for blindness, renal failure, foot amputations and MIs. Life expectancy decreased (8yrs on average) - mostly from CVD
14
Q
T2DM Definition
A
Progressive metabolic disorder = insulin deficits, increased resistance to insulin
15
Q
T2DM Epidemiology
A
Older (>40yrs), obese, certain racial groups
16
Q
T2DM Aetiology
A
Pancreatitis, surgery, trauma, cancer, pancreatic destruction (haemochromatosis, CF), cushing’s, acromegaly, hyperthyroidism, pregnancy
17
Q
T2DM RFs
A
NM=older age, ethnicity (Black African/Caribbean, South Asian), FHx, gestational diabetes, M>F
M = obesity, sedentary lifestyle, high carb diet, smoking, alcohol, hypertension
18
Q
T2DM Path
A
Repeated insulin + glucose exposure = cells in body become resistant to insulin effects = more insulin required to stimulate cells to take up and use glucose = pancreas damaged/fatigued =↓ insulin output
19
Q
T2DM Key Presentation
A
Asymptomatic usually picked up at routine medical examinations. If severe = polyuria and polydipsia (hyperglycaemia), central obesity, gradual onset
20
Q
T2DM Signs
A
Glycosuria, candidal/skin/UTI infections
21
Q
T2DM Sx
A
Tiredness, thirst (gradual onset - can be asymptomatic)
22
Q
T2DM Investigations
A
C peptide levels persist.
HbA1c
Normal <41, Pre-DM 42-47, DM >48mmol/mol
23
Q
T2DM Treatment - 1st
A
Lifestyle advice - diet, exercise, stop smoking, reduce alcohol and fat/sugar intake
1st: metformin - increase insulin sensitivity, decrease glucose production (add SGLT-2 inhibitor if CVD/heart failure)
24
Q
T2DM Treatment - 2nd
A
2nd: + SGLT-2 inhibitor (block glucose reabsorption in kidney), sulfonylurea (promotes insulin secretion), pioglitazone, DPP-4 inhibitor, (triple therapy, insulin therapy)
25
T2DM Monitoring
Annual review - check eyes, feet - wasting of small muscles of foot, clawing of toes, bleeding under hard skin, test sensation, vibration perception, ankle reflexes = high ulcer risk
26
T2DM Complications
Infections, retinopathy (risk = blood sugar control - balance with risk of hypoglycemia), peripheral neuropathy (glove and stocking), CKD, diabetic foot. Dry skin = cracks = entry for infection (moisturise), peripheral vascular disease = decreased perfusion. Nephropathy - DKD - leading cause of end-stage kidney disease = progressive kidney fibrosis = function loss - proteinuria
Hyperosmolar hyperglycaemic state
27
Hyperosmolar hyperglycaemic state
No ketones = polyuria, polydipsia, weight loss, dehydration, tachycardia, hypotension, confusion →decreased insulin insufficient to inhibit hepatic glucose production but sufficient to inhibit hepatic ketogenesis.
28
Diabetic Ketoacidosis
Serious complication of diabetes that can be life-threatening
29
DKA Aetiology
Untreated T1DM, undiagnosed DM, infection/illness, treatment errors, MI
30
DKA Path
Complete absence of insulin → unrestrained increased hepatic gluconeogenesis + decreased peripheral glucose uptake = hyperglycemia →osmotic diuresis →dehydration
Peripheral lipolysis → increase FFA → oxised to acetyl CoA → ketones = acidosis
31
DKA Signs
Hyperventilation (Kussmal’s breathing) - get rid of CO2 (reduce acid), dehydration, hypotension, tachycardia, coma, breath smell of ketones (sweet), reduced tissue turgor
32
DKA Sx
Over days, polyuria, thirst, nausea/vomiting, weight loss, weakness, abdo pain, drowsiness, confusion
33
DKA Investigations
Hyperglycemia = RPG >11mmol/L
Ketonaemia = plasma ketones >3mmol/L
Acidosis = blood pH<7.3 or bicarb <15mmol/L,
urine dipstick = glycosuria/ketonuria
34
Hyperthyroidism
Overproduction of thyroid hormones (T3/4) = thyrotoxicosis
35
Hyperthyroidism Epidemiology
Goitre >60yrs
36
Hyperthyroidism Aetiology
GIST: Grave’s Disease (mc), Inflammation (thyroiditis), Solitary toxic thyroid nodule, Toxic multinodular goitre, pituitary tumours (secondary), Iodine
37
Hyperthyroidism RFs
FHx autoimmune disease, female, smoking, amiodarone, stress
38
Graves Path
Graves = TSH-R autoAbs = uncontrolled stimulation (often brought on by pregnancy)
39
Hyperthyroidism Signs (General and Graves)
General = tachycardia, muscle wasting, fine tremor, thin hair, hair loss, possible goitre
Graves = no nodules goitre/thyroid ophthalmopathy (exophthalmos)/pretibial myxedema/hand swelling and finger clubbing.
40
Hyperthyroidism Sx
Heat intolerance, diarrhoea, wt loss, hyperphagia, insomnia, anxiety, oligo/a-menorrhea
41
Hyperthyroidism Investigations
Thyroid function tests = Primary: ↑T3/4, ↓TSH or Secondary: all ↑
Anti-TSH-R Abs (Graves), anti-TPO Abs
Radioactive uptake scan (doppler US - goitre)
42
Hyperthyroidism Treatment
1st: Carbimazole (titrate up) - blocks T3/4 production (CI in pregnancy - Propylthiouracil)
SE = agranulocytosis = depletion of WBCs (sore throat = stop taking)
2nd line = radioactive Iodine = destroys excess thyroid (CI = pregnancy) + then surgery
43
Hyperthyroidism Complications
Heart failure, osteoporosis
Thyroid storm = rapid deterioration of thyrotoxicosis + lots of T4 - systemic decompensation (AF, coma)
Tx = propylthiouracil (hepatitis risk + inhibit T4 to T3) + KI
44
Hypothyroidism
Underactivity of thyroid (primary or secondary)
45
Hypothyroidism Epidemiology
F>M, ageing, postpartum
46
Hypothyroidism Aetiology
Iodine deficiency (mc developing world), Hashimoto’s (mc developed world) = autoimmune, congenital, pituitary tumours, inflammation, postpartum, viral infection (De Quervain’s thyroiditis)
47
Hypothyroidism RFs
Female, FHx/Hx autoimmune disease, pregnancy in last 6mths, radiation to head/neck, Hx thyroid surgery/treatment
48
Hypothyroidism Pathology
Hashimoto’s = anti-TPO antibodies
Iodine deficiency = key component of T3/4.
Pituitary tumour (2ndary) = compress pituitary gland or interrupt blood flow = ↓TSH production
49
Hypothyroidism Signs
Bradycardia, slow reflexes, cold hands, goitre, pretibial myxedema, hair loss (loss of outer ⅓ of eyebrow - Hertoghe’s sign), dry skin, stiff muscles
50
Hypothyroidism Sx
Thirst, dry mouth, lack of energy, hunger, weight gain, nausea/vomiting, menstrual disturbances, irregular/heavy periods, cold intolerance, brittle hair/nails
51
Hypothyroidism Investigations
Thyroid function tests = ↑TSH, ↓free T4
Anti-TPO Abs (may also be present in Graves)
Doppler US imaging
52
Hypothyroidism Treatment
Levothyroxine (T4) - titrate up + careful with dose (can cause iatrogenic hyperthyroidism)
53
Hypothyroidism Monitoring
TFTs every 3mths until TSH stable, then annually
54
Hypothyroidism Complications
Myxoedema coma (with infection) rapidly decreasing T4 = hypothermia, unconscious, heart failure - Tx = levothyroxine, ABx + hydrocortisone (until adrenal insufficiency ruled out)
Heart failure, subfertility, miscarriage, pre-eclampsia, stillbirth, postpartum haemorrhage
55
Hyperparathyroidism
Excess Parathyroid hormone (PTH) secreted from parathyroid glands
56
Hyperparathyroidism Epidemiology
57
1o (MC) Hyperparathyroidism Aetiology
Parathyroid adenoma (mc) (or hyperplasia) - hyperparathyroid = hypercalaemia
Malignant = neoplasms (sq cell lung, breast, renal) = secrete PTHrP = ectopically mimics PTH
58
Hyperparathyroidism RFs
Female, age ≥50-60yrs (post-menopause), FHx of PHPT, multiple endocrine neoplasia (MEN) 1, 2A, or 4
2o/3o = conditions affecting Ca metabolism (2o = CKD, Vit D def, 3o = hyperplastic PTGs)
59
Hyperparathyroidism Key Pres
Commonly asymptomatic - picked up incidentally on blood tests.
Bone, Stones, Groans, Moans
60
Hyperparathyroidism Signs
Fractures, osteoporosis (bone resorption), hypertension
61
Hyperparathyroidism Sx
Non-specific - fatigue, polyuria/dipsia, constipation, abdominal pain, vomiting, confusion, depression, (bone pain + renal stones = chronic hypercalcaemia)
62
Hyperparathyroidism Investigation 1st
Serum PTH with paired corrected Ca
63
Hyperparathyroidism Other Ix
DEXA scan = osteoporosis, increase 24-hr urinary Ca excretion, abdominal X-ray = renal calculi/nephrocalcinosis, radioisotope scanning = 90% sensitive to adenomas
64
Hyperparathyroidism DDx
Other causes of hypercalcaemia - malignancy (high serum PTH rules out), PTH dependent/independent
65
Hyperparathyroidism Treatment
1o = Surgery - remove adenoma or parathyroidectomy of all 4 glands, bisphosphonates (not affect serum Ca but preserve bone density = reduce fracture risk), Cinacalcet (Ca-sensing receptor agonist) = reduce PTH secretion + tf serum Ca (if no surgery)
2o = treat underlying cause, 3o = surgery
66
Hyperparathyroidism Complications
1o = osteoporosis, renal impairment and calculi, pseudogout, pancreatitis, CVD, acute severe hypercalcaemia = IV fluids + bisphosphonates
67
2o Hyperparathyroidism Aetiology
Physiological response to low [Ca++] - compensatory hypertrophy of all glands (CKD/Vit D def) - hypocalcaemia = hyperparathyroidism
68
3o Hyperparathyroidism Aetiology
Years of 2o hyperPTH (mc = CKD) glands act autonomously = release PTH not -ve feedback = increase PTH regardless of [Ca]
69
Hypoparathyroidism
Deficiency of PTH secreted
70
Hypoparathyroidism Aetiology
Secondary to parathyroidectomy, congenital, Mg deficiency, vit D deficiency = less Ca, autoimmune - Di George syndrome
71
Hypoparathyroidism RFs
Hx thyroid/parathyroid surgery, hypomagnesaemia, moderate/chronic maternal hypercalcaemia
72
Hypoparathyroidism Signs
Hypocalcemia signs - convulsion, arrhythmias, tetany, Chvostek’s sign = tap over facial nerve in parotid gland region = twitching of ipsilateral facial muscles, Trousseau’s sign = carpopedal spasm induced by inflation of BP cuff to 20mmHg >systolic BP, ECG - prolonged QT interval, chronic = depression, cataracts
73
Hypoparathyroidism Sx
Muscle spasms, tetany, twitching, cramping, diarrhoea, anxiety, dry hair
74
Hypoparathyroidism Ix 1st
Serum Ca + Mg, plasma intact PTH, serum albumin
75
Hypoparathyroidism Tx
Ca supplement + calcitriol (active vit D), synthetic PTH
76
Pseudohypoparathyroidism
Abnormality in Gz protein on PTG - resistance to PTH (low Ca, High P + PTH)
77
Pseudohypoparathyroidism Ix
Urinary cAMP + P following infusion of PTH:
Type 1 = neither increase
Type 2 = only cAMP rises
(in hypoPTH = cAMP + P increased)
78
Pseudohypoparathyroidism Signs/Sx
Short stature, short metacarpals (4th/5th), subcutaneous calcification, sometimes low IQ
79
Pseudohypoparathyroidism Tx
Same as normal hypoPTH = Ca supplement + calcitriol (active vit D), synthetic PTH
80
Pseudopseudohypoparathyroidism
Same phenotype as pseudo but Ca metabolism normal
81
AVP Deficiency (Diabetes Insipidus)
Not enough AVP (ADH) produced or reduced response to ADH = inability to concentrate urine
82
AVP Deficiency Cranial Causes/RFs
Pituitary surgery, head trauma, craniopharyngioma, congenital defect in ADH gene, idiopathic
83
AVP Deficiency Nephrogenic Causes/RFs
Drugs (LiCl), hypokalaemia, hypercalcaemia, renal tubular acidosis, sickle cell disease, ADHR mutation
84
AVP Deficiency Path (Cranial and Nephrogenic)
Cranial = too little ADH from posterior pituitary
Nephrogenic = kidney does not respond to ADH
Less ADH/response to ADH = ↑H2O loss in urine; dilute high volumes
85
AVP Deficiency Signs
Postural hypotension, dilute urine, dehydration = dry mucous membrane, prolonged capillary refill time), hypernatremia
86
AVP Deficiency Sx
Polyuria (>3L/day), nocturia, polydipsia, severe dehydration, confusion, coma
87
AVP Deficiency 1st Ix
Low urine osmolality, high/normal serum osmolality, >3L on 24hr urine collection
88
AVP Deficiency GS Ix
Water deprivation test (desmopressin stimulation test) = avoid all fluids for >8hrs before (water deprivation) the urine osmolality measured
89
AVP Deficiency Other Ix
Cranial MRI, genetic testing, U+Es (rule out electrolyte abnormalities)
90
AVP Deficiency Cranial Tx
Desmopressin - replace absent ADH
91
AVP Deficiency Nephrogenic Tx
Drink plenty of water, high dose desmopressin, thiazide diuretics = more Na secretion in DCT = increased water loss = reduce GFR, NSAIDs = reduce GFR - inhibit prostaglandin synthesis (locally inhibit ADH action)
92
AVP Deficiency Complications
CDI + desmopressin = serum Na - risk of hyponatremia
93
Acromegaly
Prolonged elevated levels of growth hormone (GH) - post-epiphyseal fusion
94
Acromegaly Epidemiology
Rare 3/mill/yr, M=F
95
Acromegaly Aetiology
GH-secreting pituitary adenoma
96
Acromegaly RFs
FHx MEN, McCune-Albright syndrome, Carney complex
97
Acromegaly Path
Pituitary produces more growth hormone - to liver = makes more IGF-1 →usual -ve feedback inhibiting GH secretion by producing somatostatin (acts on somatotrophs) does not work
98
Acromegaly Signs
Hypertension, heart failure, galactorrhoea, bitemporal hemianopia, carpal tunnel syndrome, macroglossia, prognathism (protruding lower jaw), enlarged hands/feet (can they take rings off?), skin thickening, interdental separation
99
Acromegaly Sx
Sweating, headaches, visual changes (tumour).
Systemic = appearance changes, wt gain, fatigue, joint pain, voice changes, skin tags.
Prolactin symptoms = amenorrhoea, galactorrhoea, ED, reduced libido, infertility
100
Acromegaly Investigations
1st line: IGF-1 > normal range
Gold: 75gm oral glucose tolerance test = if GH level does not reduce
Other: MRI of pituitary (adenoma), pituitary function
101
Acromegaly Treatment
1st line = transsphenoidal pituitary surgery (microadenoma <1cm = 90%, macroadenoma >1cm=50%)
Radiotherapy - conventional multi-fractional, stereotactic single fraction = less radiation to surrounding tissues - loss of pituitary function, damage to local structures (eye nerves), control not always achieved
Medication - dopamine agonists (Ads = no hypopit, rapid, oral. Dis = side effects, relatively ineffective), somatostatin analogues, Pegvisomant (GH analogue) = very effective but £££ = block GH effect on liver
102
Acromegaly Complications and Prognosis
Hypertension, diabetes, cardiomyopathy, colorectal cancer, arthritis, sleep apnea, carpal tunnel, sleep apnea, hypopituitarism, psychosocial impacts
Decreased life expectancy
103
Hyperprolactinemia
High serum prolactin (lactotrophs)
104
Hyperprolactinemia Epidemiology
Females>Males
105
Hyperprolactinemia Aetiology
Macro/micro-prolactinoma, non-functioning pituitary tumour, antidopaminergic drugs + ecstasy (mc), hypothyroidism, PCOS, renal failure, stress, chest wall injury
105
Hyperprolactinemia Signs
Men = low testosterone, female = low oestrogen
106
Hyperprolactinemia Sx
Amenorrhoea, infertility, galactorrhoea, low sex drive (M+F), headache, bi-temoral hemianopia, CSF leak, ED, gynecomastia
107
Hyperprolactinemia Investigations
↑↑ serum prolactin
108
Hyperprolactinemia Tx
1st line = dopamine agonists (Cabergolin) = tumour shrinkage - inhibitor of prolactin
109
1o Adrenal Insufficiency
Addison’s = decreased adrenocortical hormone production
110
Adrenal Insufficiency Epidemiology
1o: Addison’s (autoimmune destruction - 21-hydroxylase) mc in developed world , TB in developing
2o: mc = iatrogenic (steroids), others = adrenal mets (lung, liver, breast), adrenal haemorrhage (meningococcal septicaemia)
111
Adrenal Insufficiency Aetiology
Autoimmune adrenalitis (mc), CAH, metastasis, infection (TB), infiltration (amyloid)
112
Adrenal Insufficiency RFs
Hx TB, postpartum bleed, cancer, steroids. FHx autoimmune, congenital diseases (MEN), female
113
Adrenal Insufficiency Path (Addison's and HPA suppression)
Addison's: Auto ABs destroy adrenal cortex = ↑ACTH→stimulate POMC (melanocytes) = hyperpigmentation, ↓adrenal hormones
HPA suppression: ↓ACTH + ↓adrenal hormones + no hyperpigmentation
114
Adrenal Insufficiency Signs
Pigmentation (high ACTH - 1o) and pallor, postural hypotension (↓aldosterone), low Na, high K, eosinophilia, borderline elevated TSH, hypoglycemia, vitiligo
115
Adrenal Insufficiency Sx
Fatigue, weight loss, fainting, confusion, body aches, abdo pain, vomiting
116
Adrenal Insufficiency 1st Ix
Hyponatremia (due to ↓aldosterone), Hyperkalemia (due to ↓aldosterone), ↓cortisol
ATCH: ↑in 1o, ↓/normal in 2o
↑Renin in Addison’s, ↓Aldosterone in Addison’s
117
Adrenal Insufficiency GS Ix
Synacthen test - tests adrenal reserves (cortisol not↑)
118
Adrenal Insufficiency Other Ix
For causes: 1o = adrenal Abs (-ve then CT scan, genetics)
2o = MRI of pituitary then genetics
119
Adrenal Insufficiency Tx
1o = Hydrocortisone (replace cortisol) - according to weight (adults) - higher dose in am (adjust according to symptoms/signs of under/over -dose) - stressed/intense exercise = extra 5mg
Mineralocorticoid (replace aldosterone) - hypertension = reduce (not stop), increase if sweating
120
Adrenal Insufficiency Monitoring
Must carry steroid emergency card, Mineralocorticoid = monitor U+E, BP, salt craving
121
Adrenal Insufficiency Complications + Prognosis
Adrenal crisis = severe insufficiency ESP hypocortisolemia →n+v renal failure, LOC
Tx = immediate hydrocortisone + IV saline + dextrose if hypoglycemia
Lower quality of life and lower life expectancy
122
3o Adrenal Insufficiency
Suppression of HA - medications (steroids, opioids)
123
Cushing's Syndrome
Chronic excess of glucocorticoids
124
Cushing's Syndrome Epidemiology
F>M
125
Cushing's Syndrome Aetiology
ACTH dependent = Cushing's Disease - ACTH secreting pituitary adenoma (mc), ectopic ACTH
ACTH independent = adrenal adenoma, iatrogenic - steroid use (mc)
126
Cushing's Syndrome Signs
Moon face, buffalo hump (enlarged fat pad on upper back)
Hirsutism (male pattern hair on women)
Easy bruising, poor skin healing, abdominal striae
Central obesity, proximal limb muscle wasting Excess ACTH = hyperpigmentation, plethoric complexion
127
Cushing's Syndrome Sx
Headaches, visual field changes
128
Cushing's Syndrome 1st Ix
Rule out oral steroids (stop them), random serum cortisol↑(12am: normally lowest here)
Dexamethasone suppression test (overnight) - essentially cortisol (healthy = -ve feedback HPA axis + ↓ cortisol:
00:00 = Give Dexa and measure cortisol (before give dex), 08:00 = measure cortisol (non-Cushing’s = suppression >50nmol/L, Cushing’s = little/no suppression)
129
Cushing's Syndrome GS Ix
1st line +ve = measure plasma ACTH: ↑=ACTH dependent - look for cushing’s disease on pituitary MRI; ↓=ACTH independent - adrenal adenoma
130
Cushing's Syndrome Tx
Cushing’s = transphenoidal resection or bilateral adrenalectomy (Nelson’s syndrome)
Adrenal adenoma = adrenalectomy, ectopic = surgical removal
131
Cushing's Syndrome Complications
Hypertension, osteoporosis, DM, cataracts, myopathy
132
Hyperaldosteronism
Primary hyperaldosteronism - independent of RAAS
Secondary - excessive renin
133
Hyperaldosteronism Aetiology
1o: 1/3 = adrenal adenoma (Conn’s), 2/3 = bilateral adrenal hyperplasia
2o: renal artery stenosis (atherosclerosis), heart failure, liver cirrhosis/ascites
134
Hyperaldosteronism RFs
FHx of PA, early hypertension onset/stroke
135
Hyperaldosteronism Path
1o: ↑↑aldosterone = ↑↑Na + H2O + ↓↓K = hypertension and hypokalemia
2o: disproportionately lower kidney BP = excessive renin released = stimulates ↑ aldosterone release
136
Hyperaldosteronism Signs
Hypertension, hypokalemia (mc with Conn’s), metabolic alkalosis
137
Hyperaldosteronism 1st Ix
Aldosterone:Renin ratio (ARR) = screening-
1o =↑ald + ↓renin
2o =↑ald + renin
138
Hyperaldosteronism GS Ix
↑serum aldosterone not suppressed w/0.9% saline or fludrocortisone, hypokalemic ECG
139
Hyperaldosteronism Other Ix
CT/MRI = adrenal tumour or hyperplasia, renal artery imaging (doppler, CT angiogram) = renal artery stenosis, adrenal vein sampling
140
Hyperaldosteronism Tx
Adrenal adenoma = surgery (adrenalectomy)
Hyperplasia = aldosterone antagonist (Spironolactone)
141
Hyperaldosteronism Complications
Most common cause of 2o hypertension (often undiagnosed)
142
Syndrome of Inappropriate ADH (SIADH)
Inappropriately released ADH (dilute euvolemia) from post pituitary
143
SIADH Aetiology
Tumours (SLCL, prostate, pancreatic), Infection/inflammation (TB, meningitis, HIV), Abscesses, Drugs (SSRIs, carbamazepine), Head trauma, Post-op
144
SIADH RFs
Age>50yrs, pulmonary conditions, nursing home residence, post-op, Hx diuretic use
145
SIADH Path
↑ADH produced by hypothalamus and secreted by PPG = stimulate H2O reab in kidney CDs = dilute blood + ↓[Na] (hyponatremia) = more concentrated urine
146
SIADH Signs
Brain stem herniation through Foramen Magnum (↑Na =↑compensatory H2O = enters skull + ↑ICP = hyponatremia encephalopathy), cognitive impairment, pulmonary/peripheral oedema
147
SIADH Sx
Headache, fatigue, muscle aches, cramps, confusion, severe = seizures and reduced consciousness, vomiting
148
SIADH 1st Ix
↓Na serum, normal K serum,↑urine osmolality
149
SIADH GS Tx
Hyponatremia, low plasma osmolality40mmol/L despite normal salt intake, euvolemia, normal thyroid + adrenal function (short synacthen test - exclude adrenal insufficiency)
150
SIADH DDx
Adrenal insufficiency, Hx diuretic use, excessive H2O intake, C/A-KD, heart failure, liver disease
Na (salt) depletion = give 0.9% saline + SIADH = serum not normalise, Na depletion = serum normalises
151
SIADH Tx
Fluid restriction + hypertonic saline (concentrate blood), treat underlying cause (tumour excision), chronic = drugs (furosemide, ADH antagonist)
152
Hypokalaemia
Low Serum K <3.5mmol/L, <2.5mmol/L = emergency
153
Hypokalaemia Aetiology
Increased excretion: drugs (thiazide, loop), renal disease, GI loss, increased aldosterone (Conn’s).
Reduced dietary intake (dietary deficiency).
Shift to intracellular (drugs - insulin, salbutamol)
154
Hypokalaemia Signs
Arrhythmias (Esp AF), muscle paralysis, rhabdomyolysis, hypotonia, hyporeflexia
155
Hypokalaemia Sx
Fatigue, generalised weakness, muscle cramps/pain, palpitations (can be aSx)
156
Hypokalaemia Ix
↓[K] <3.5mmol/L, FBC, U+Es, ECG
157
Hypokalaemia ECG
Main = ST depression,
Others = flattened/inverted T waves, U waves, prolonged PR interval, atrial/ventricular tachyarrhythmias
158
Hypokalaemia Tx
K replacement, aldosterone antagonist
159
Hyperkalaemia
High Serum K >5.5mmol/L
160
Hyperkalaemia Aetiology
Increased intake (IV/diet).
Decreased kidney excretion:↓GFR in A/CKD, adrenal insufficiency (principal cells secrete less K), drugs (ACE-i, NSAIDs)
Shift to extracellular (metabolic acidosis, rhabdomyolysis)
161
Hyperkalaemia Path
↑K decreases threshold AP = easier depolarisation = abnormal heart rhythms
162
Hyperkalaemia Signs
ECG changes, arrhythmias, hyperreflexia, reduced power, signs of underlying cause
163
Hyperkalaemia Sx
MURDER:
Muscle weakness
Urine (oliguria)
Resp distress
Decreased cardiac contractility
ECG changes
Reflexes = hyperreflexia or flaccid
Fatigue, chest pain, weakness, palpitations
164
Hyperkalaemia Ix
↑[K] >5.5mmol/L (U+Es), FBC, urine osmolality, ECG
165
Hyperkalaemia ECG
Main: tall/tented T waves (narrow base), widened QRS, absent P waves
Others: prolonged PR interval, shortened QT interval
166
Hyperkalaemia Tx
Urgent = 30ml 10% calcium gluconate IV STAT (cardiac protective)
Non-urgent = insulin (shifts K into cells) + dextrose (glucose - prevent hypoglycaemia) + consider Salbutamol (shifts K)
W/ heart problems = stabilise cardiac membrane, then insulin and dextrose
167
Hypocalcaemia
Low serum Ca<8.5mmol/L
168
Hypocalcaemia Aetiology
CKD (↓VitD activation), severe Vit D deficiency, hypoPTH, drugs (bisphosphonates, calcitonin), acute pancreatitis
169
Hypocalcaemia Signs
↑Muscle tone + contractions, Trousseau + Chvostek signs, hypotension
170
Hypocalcaemia Sx
Can be aSx
Muscle cramps, abdominal pain, carpopedal spasming
171
Hypocalcaemia Ix
↓Ca (corrected or free), ECG - prolonged QT/ST segments, arrhythmias
172
Hypocalcaemia Tx
Normalise Ca levels - Ca gluconate, Vit D supplement
173
Hypocalcaemia Complications
Osteopenia, osteoporosis, cardiac arrhythmias, tetany, seizures
174
Hypercalaemia
High serum Ca>10.5mmol/L
175
Hypercalaemia Aetiology
MC = hyperPTH, bone malignancy
Other = drugs (thiazides), hyperthyroid, dehydration, excess Ca intake, tumours
176
Hypercalaemia Signs
Polyuria, ↓muscle tone + contractions (Ca inhibits fast Na influx)
177
Hypercalaemia Sx
Can be aSx
Bones, Stones, Groans, Moans (psycho) = Bone pain, kidney stones, abdominal pain/nausea, depression, anxiety, coma, insomnia
178
Hypercalaemia Ix
↑Ca (corrected for albumin or measure free ionised Ca)
ECG - short QT, bradycardia, AV block, Osborn wave
179
Hypercalaemia Tx
Lower Ca levels = rehydrate (↑Ca urinary excretion), loop diuretics (inhibit Ca reab), glucocorticoids (↓gastro Ca ab), bisphosphonates/calcitonin (inhibit osteoclasts), dialysis = if renal failure
180
Hypercalaemia Complications
Hypercalciuria = kidney stones
Osteoporosis (depletion of Ca stores), renal failure, cardiac arrhythmias, confusion, dementia, coma
181
Thyroid Carcinoma
Tumours derived from thyroid follicular epithelium (except medullary - functional parafollicular C cells)
182
Thyroid Carcinoma Epidemiology
Papillary (mc - 70%), follicular (25%), anaplastic, lymphoma, medullary cell
183
Thyroid Carcinoma Aetiology
Gain of function mutation in signalling pathways (except medullary)
184
Thyroid Carcinoma RFs
FHx, head/neck irradiation, F, age
185
Thyroid Carcinoma Met Sites
Met sites mc; lung (50%), bone (30%), liver (10%), brain (5%)
Compression at local site = Sxs
186
Thyroid Carcinoma Signs
Hypothyroidism, thyroid nodules - hard + irregular
187
Thyroid Carcinoma Sx
Hoarse voice, trouble swallowing (local compression), hypothyroidism (weight gain, fatigue, cold intolerance)
188
Thyroid Carcinoma 1st Ix
TFTs
189
Thyroid Carcinoma GS Ix
Fine Needle Aspiration Biopsy
190
Thyroid Carcinoma Other Ix
Ultrasound
191
Thyroid Carcinoma Tx
Papillary and follicular = thyroidectomy and radiotherapy.
Anaplastic = palliative mostly (worst prognosis - often metastasises)
192
Carcinoid Tumours and Syndrome
Malignant tumours of enterochromaffin cells
193
Carcinoid Tumours and Syndrome Aetiology
Most commonly arises from GI tract (SI - terminal ileum, appendix), then lungs, liver, ovaries, thymus
194
Carcinoid Tumours and Syndrome RFs
MEN-1
195
Carcinoid Tumours and Syndrome Path
Tumours of enterochromaffin cells produce serotonin/5-HT
Carcinoid tumours = only neoplastic cells (no Sx/v.little)
Carcinoid syndrome - metastasises to liver = Sx
196
Carcinoid Tumours and Syndrome Signs
Telangiectasia (dilation of capillaries = small red/purple clusters (spidery)
Tricuspid incompetence (valve lesion)
Heart failure, palpitations, bronchospasm
197
Carcinoid Tumours and Syndrome Sx
Wheezing, abdominal pain
Mets to liver = diarrhoea + flushing (warmth, erythema)
198
Carcinoid Tumours and Syndrome Ix
↑5-hydroxyindoleacetic acid (major metabolite of 5HT), metabolic panel, LFTs
CT/MRI = locate tumour, liver US = confirm mets
199
Carcinoid Tumours and Syndrome Tx
Surgically excise 1o tumour (definitive), Somatostatin (SST) analogue (octreotide) can block tumour hormones
200
Carcinoid Tumours and Syndrome Complications
Carcinoid crisis - life threatening, Sx constellation, Tx SST analogue high dose
201
Phaeochromocytoma
Adrenal medullary tumour (chromaffin cells) secretes catecholamines (NAd, Adr)
202
Phaeochromocytoma Epidemiology
V.rare, 30-40% genetic, 10% = bilateral, 10% cancerous, 1-% outside adrenal gland
203
Phaeochromocytoma Aetiology
MEN 2a/b, neurofibromatosis I (tumour deposited along nerve myelin sheath), Von-Hippel Lindau Disease
204
Phaeochromocytoma RFs
Older M
205
Phaeochromocytoma Path
Unregulated secretion of excessive adrenaline = stimulation of sympathetic nervous system
206
Phaeochromocytoma Signs
Hypertension, postural hypotension, tachycardic, palpitations, pallor
207
Phaeochromocytoma Sx
Headaches, sweating, anxiety, tremor
Often episodic - Adr released in bursts = intermittent Sx
208
Phaeochromocytoma Ix
↑plasma metanephrines + normetanephrines (more sensitive than NAd/Adr = longer ½ life)
Urinary catecholamines, CT imaging - tumour, genetic testing
209
Phaeochromocytoma Tx
Alpha blockers (phenoxybenamine), then beta blocker (atenolol) = prevents reactive vasoconstriction
Surgery if possible - excise tumour
210
Phaeochromocytoma Complications
Hypertensive (HTN) crisis (180/120 + BP) = give Phentolamine (alpha blocker)
