Endocrine Hypertension and Calcium Disorders Flashcards
1
Q
What target organs are damaged by hypertension
A
- Heart
- Kidneys
- Eyes
- Brain
2
Q
How is the heart affected by hypertension
A
- can cause left ventricular hypertrophy
- lead to heart failure
- puts it at risk of MI
3
Q
How is the kidney affected by hypertension
A
- Small shurnken kidneys
- proteinuira
4
Q
How are the eyes affected by hypertension
A
- hypertensive retinopathy
- palipoedema
5
Q
How are is the brain affected by hypertension
A
- intracerebral haemorrhage
6
Q
What are the grades of hypertensive retinopathy
A
Grade 1 – silver (copper) wiring
Grade 2 – arteriovenous nipping
Grade 3 – flame shaped haemorrhages + exudates
Grade 4 - papilloedema
7
Q
What are the secondary causes of hypertension
A
Cardiac:
- Coarctation
Renal: - CKD, - glomerulonephritis, - renovascular disease(renal artery stenosis) - might hear a renal bruit
Endocrine:
- Conns,
- Cushings,
- Phaeochromocytoma
- Acromegaly
- Hypothyroidism
- Hyperparathyroidism
8
Q
What are the risk factors for secondary hypertension
A
Younger Age
Strong Family History
Requirement for multiple anti-hypertensives (due to resistant hypertension)
Physical signs of secondary hypertension:
- Renovascular, endocrine
Other factors: Electrolytes, glucose, calcium
9
Q
What is conns syndrome (primary hyperaldosteronosim)
A
- excess production of aldosterone, independent of the RAAS system causing increase in sodium and water retention and decreases renin release
- hyperaldosteronism which leads to hypertension and hypokalemia
10
Q
What are the causes of conns syndrome
A
- adrenal adenoma
- bilateral adrenal hyperplasia
11
Q
What investigations should you do when investigating conns syndrome
A
Electrolytes:
- hypokalaemic alkalosis
do a paired renin aldosterone level
Elevated serum aldosterone
Suppressed plasma renin
Image the adrenals with CT
Adrenal
vein sampling to differentiate unilateral from bilateral adrenal disease
12
Q
what age group does conn’s disease occur in
A
- Aged 40-60 years old
13
Q
describe the hypertension experienced by conns disease
A
Resistant hypertension: more than 3 agents
Severe hypertension: >160 mmHg systolic or 100 mmHg diastolic
14
Q
Patients with conns disease are not…
A
always hypokalaemic
15
Q
How do you manage conns disease
A
Unilateral adrenal adenoma:
- Surgery
Bilateral adrenal hyperplasia:
- aldosterone antagonist
▪ eg eplerenone, spironolactone
16
Q
how can cushing syndrome present in hypertension
A
Exogenous
- prednisolone therpay
Endogenous
- Cortisol excess
- ACTH - dependant
- ACTH - independant
17
Q
What happens in a phaecytochroma
A
excess catecholamines
-tumour of adrenal medulla
18
Q
What is the adrenal medulla regulated by
A
Adrenal medulla is regulated by direct cholinergic input from the splanchnic nerve
19
Q
What do chromaffin cells secrete
A
Chromaffin cells secrete adrenaline > noradrenaline > dopamine
20
Q
What do catecholamines activate
A
Tachycardia
Vasoconstriction
Hypertension
Fight, fright, flight response
21
Q
What is the 10% rule in phaechromocytoma
A
10% extra adrenal
10% malignant
10% familial endocrine neoplasia syndromes
22
Q
List what is the types of familial endocrine neoplasia syndromes
A
- Von hippel lindau disease
- MEN 2
- SDH mutation
23
Q
Describe Von hippel lindau disease
A
- cerebellar haemangioma
- retinal angiomata
- renal cell carcinoma
- phaeochromocytoma
24
Q
Describe MEN2
A
- Medullary carcinoma thyroid
- Phaeochromocytoma
- hyperparathyroidism
25
What diseases are associated with an increased risk of phaeochromocytoma
- Von hippel lindau disease
- MEN 2
- SDH mutation
26
What does A1 and A2 alpha receptors do
A1: vasoconstriction
| A2: vasoconstriction
27
What do B1 and B2 receptors do
B1: increased heart rate,
increased cardiac contractility
B2: vasodilatation, increase hepatic glucose production, increase renin secretion
28
name some alpha receptor blockers
Doxazosin
| Phenoxybenzamine
29
Name some beta receptor blockers
Propranolol
| Atenolol
30
What investigations do you do for a phaeochromocytoma
24 hour collection (3 times) urine catecholamines / metanephrines
Imaging of the abdomen CT or MRI
MIBG scan
(Screening for endocrine neoplasia syndromes)
31
How do you manage a phaeochromocytoma
Surgery
- alpha blockage pre-op: phenoxybenzamine (used before beta blocker to avoid crisis from unopposed alpha-adrenergic stimulation) + beta blocker if heart disease or tachycardia
- malignant cases: Chemotherapy and therapeutic MIBG
- post-op: do 24 hour urine metanephrine 2 weeks post op, monitor blood pressure
Follow up
- lifelong malignant recurrence may present late; genetic screening
32
what hormone does GH counteract the effective of
GH is a stress hormone and counters the effects of insulin
33
what adenoma can cause growth hormone excess
- Secretory adenoma of the pituitary somatotroph cells
34
What investgiations do you do to investigate growth hormone excess
Oral glucose tolerance test
Failure of suppression of growth hormone after 75 grams of
glucose
IGF-1
MRI pituitary fossa
35
What is the management of growth hormone excess
Trans-sphenoidal resection
Post op radiotherapy
```
Medical management
Somatostatin analogues
▪ Octreotide
Growth hormone receptor antagonist
▪ Pegvisomont
```
36
What happens with serum calcium falls
- PTH increases
- leads to increase in activation of vitamin
- increase in movement of calcium from the bones into the blood
37
What is the differential diagnosis of polyuria and polydipsia?
- diabetes mellitus
- diabetes inspedius - can be cranial or nephrogenic
- hypercalemia
38
if serum PTH is risen in a high calcium what does that mean
hyperparathyroidism
39
what happen if serum PTH is low and there is high calcium
- most likely not related to the parathyroid gland and can be due to malignancy
- due to excess PTHrp produce by the tumour
40
How do you manage hypercalcaemia
1. Give 5% dextrose
2. Give IV saline and pamidronate
3. Give IV saline alone
4. Give 5% dextrose and pamidronate
5. Give IV saline and calcitonin
41
How do you investigate hyperparathyroidism
Localise the parathyroid adenoma using
- USS
- SestaMibi Scan
- Parathyroid venous sampling
42
How do you manage cancer
Treat cancer
| Bisphosphonates
43
Where is phosphate predominantly found
- Predominantly bound in bone (85%) and some in the serum
44
What happens to phosphate at the kidney
When it is in the blood and not bound to protein it is filtered by the kidney and it is either:
- reabsorbed at the PCT
- reabsorbed via the Na/PO4 co-transporter in the loop of Henle
- excreted as a urinary buffer
45
How does PTH reduce the phosphate reabsorption in the loop of Henle
- PTH inhibits the Na/PO4 co transporter
| - this reduces phosphate reabsorption in the loop of Henle
46
Where is calcium in the body
- most in the bone 99.9%
- rest in the serum - 50% protein bound, 40% ionised, 10% in complexes with phosphate/citrate
-
47
How much of calcium is biologically active
2.2-2.6mmol/L
48
How is calcium filtered in the kidney
- most is reabsorbed at the PCT
- further absorption in the thick ascending loop of Henle where some potassium leaks back into the lumen via Na/K/2Cl co-transporter
- the resulting electrochemical gradient drives paracellular absorption of sodium, magnesium and calcium
49
what do loop diuretics cause in terms of calcium
- Hypocalcaemia
50
What do thiazide diuretics cause in terms of calcium
- hypercalcaemia
| - increases calcium reabsorption in DCT useful for treating idiopathic hypercalciuria and stone formation
51
How does PTH affect calcium reabsorption
- increase calcium reabsorption in the DCT
52
What happens to calcium in acidaemia
- decrease binding to protein so there is an increase in ionised calcium
53
What happens to calcium in alkalaemia
- increase binding to protein therefore there is a decrease in ionised calcium
54
What is parathyroid hormone secreted in response to
- secreted in response to decreased ionised calcium
55
Where is parathyroid hormone produced
- from 4 parathyroid glands behind the thyroid
56
What controls parathyroid hormone
- controlled by negative feedback of calcium
57
What is the function of parathyroid hormone
- increases osteoclast activity this releases calcium and phosphate form the bones
- increases calcium and decreases phosphate reabsorption in the kidney
- increases 1,25-dihydroxyvitamin D3 production
58
Where is calcitonin produced
- secreted by parafollicular cells (C-cells) of the thyroid
59
what is calcitonin released in response to
increased ionised calcium
60
What does calcitonin do
- counteracts the effects of PTH and increase secretion of sclerotin by osteocytes
61
describe how vitamin D is produced
- 7-dehydrocholesterol is turned into provitamin D from the skin and UV radiation
- vitamin D is then converted into 25-hydroxyvitamin D (liver) unregulated
- 25-hydroxyvitamin D is turned to 1,25-dihydroxyvitamin D in the kidney and this is regulated
62
What are the actions of 1,25-dihydroxyvitamin D
- intestine - increases calcium and phosphate absorption
- Kidney - increases calcium and phosphate reabsorption
- Bone - stimulates osteoclast to increase bone reabsorption to calcium and phosphate
63
How does hypercalcaemia present
- Bones - pain
- stones - renal biliary
- abdomen groans - abdominal pain, nausea and vomiting, constipation
- psychic moans - confusion, cognitive dysfunction, depression, anxiety, insomnia, lethargy, coma, hyporeflexia
- thrones - polyuria, polydipsia
64
What does hypercalcaemia look like on an ECG
- Short QT interval
65
What are the causes of hypercalcaemia
Hyperparathyroidism
- primary
- secondary
- tertiary
- malignant
- familial hypocalciuric hypercalcaemia
- excess action of vitamin D
- excess calcium intake
- drugs
- thryotoxicosis
- Addison's disease
66
What is the most common cause of hypercalcaemia
primary hyperparathyroidism
67
What causes primary hyperparathyroidism
- solitary adenoma
- hyperplasia of all glands
- parathyroid cancer
68
What causes secondary hyperparathyroidism and what happens in it
- reduced vitamin D intake and CKD (no Hypercalcaemia)
| - decreased calcium and increased PTH
69
What happens in tertiary hyperparathyroidism
Prolonged secondary hyperparathyroidism
- glands act autonomously due to hyperplasia/adenoma
- causes increase calcium from increased secretion of PTH unlimited by negative feedback control
70
What cancers can cause malignant hyperparathyroidism
- squamous cell cancer
- breast cancer
- renal cell cancer
71
describe how malignant hyperparathyroidism happens
- parathyroid-related protein (PTHrP) is produced by the tumour, this mimics PTH resulting in increased calcium
- PTH is decreased as PTHrP is not detected in assay
72
What does familial hypocalciruic hypercalcaemia due to
- autosomal dominat mutation in calcium sensing receptors in PTH glands and cells in thick ascending limb
- this lead to increase in serum calcium and decrease in excretion
- the increase inc calcium is detected as normal due to defect of the receptors so PTH increases due to loss of negative feedback
73
what can cause excess action of vitamin D
- Iatrogenic or self-administered excess
- granulomatous diseases such as sarcoidosis, tuberculosis
- lymphoma
74
What causes excessive calcium intake
- milk-alkali syndrome
75
What drugs cause hypercalcaemia
- thiazide diuretics
- vitamin D analogues
- lithium
- Vitamin A
76
What do bloods look like in
- calcium
- PTH
- phosphate
- ALP
for
- primary hyperparathyroidism
- secondary hyperparathyroidism
- tertiary hyperparathyroidism
- malignant hyperparathyroidism
- familial hypocalciuric hypercalcaemia
Primary Hyperparathyroidism
- calcium = raised
- PTH = raised
- phosphate = decreased
- ALP = raised
Secondary hyperparathyroidism
- calcium = lowered
- PTH = raised
Tertiary hyperparathyroidism
- calcium = raised
- PTH = double raised
Malignant hyperparathyroidism
- Calcium - raised
- PTH - lowered
familial hypocalciuric hypercalcaemia
- Calcium = raised
- PTH = raised
77
What does a DEXA scan look like in hypercalemia
- subperiosteal erosions or cysts
- brown tumours of phalanges
- Acro-osteolysis
- Pepper pot skull
78
What does end organ damage to hypercalaemia look like
- Bone – osteoporosis
- Renal – calculi, impairment, nephrocalcinosis
- Joints – chondrocalcinosis, pseudogout
- Pancreas – pancreatitis
79
Acute hypercalcaemia is greater than..
>3.5mmol/L
80
How do you manage acute hypercalcaemia
1. IV saline and a loop diuretic
2. Bisphosphonates IV -e.g. pamidronate
3. Calcitonin - if no response to IV bisphosphonates
4. glucocorticoids - prednisolone 40mg/day
81
How do you treat mild hyperparathyroidism
- increase fluid intake to prevent stones
- avoid thiazides
- high calcium and vitamin D diet
- review 6 monthly
82
What surgery can you do for hyperparathyroidism
Excision of adenoma or partial/total parathyroidectomy
83
What are the indications for surgery in hyperparathyroidism
- increase in serum or urinary calcium
- bone disease
- osteoporosis
- renal calculi
- decreased renal function
- aged less than 50 years
84
What are the complications that result from surgery in hyperparathyroidism
- hypoparathyroidism
- recurrent laryngeal nerve damage (hoarse voice)
- symptomatic hypocalcaemia
- recurrence of adenoma
85
What is the medical treatment in hyperparathyroidism
- HRT
- bisphosphonates to inhibit bone reabsorption
- calcium sensing receptor agonists - to reduce PTH secretion
86
What are the side effects of calcium sensing receptor agonists
- myalgia
| - decrease testosterone
87
How does hypocalcaemia present
- Chvostek's and Trousseau's signs
- hyperreflexia
- spontaneous twitching
- muscle cramps
- tingling and numbness
- anxiety
- tetany
88
What is the ECG of hypocalcaemia
- Long QT interval
| - Small T waves
89
Name the causes of hypocalcaemia
- hypoparathyroidism
- drugs
- CKD
- vitamin D deficiency
- acute pancreatitis - inhibition of bone reabsorption
- low plasma albumin - liver disease and malnutrition
90
Describe how primary hypoparathyroidism causes hypocalcaemia
- due to gland failure e.g. autoimmune, congenital (DiGeorge syndrome), idiopathic
91
Describe how secondary hypoparathyroidism causes hypocalcaemia
- radiation
- thyroidectomy
- parathyroidectomy
- severe hypomagnesaemia (PPI-induced, magnesium is required for PTH secretion)
92
Describe how Pseudo hypoparathyroidism causes hypocalcaemia
- failure of target cell response to PTH
| - e.g. overactivity of calcium receptor may lead to desensitisation
93
What are the signs of pseudo hypoparathyroidism
- 4th and 5th metacarpals
- round face
- short stature
- calcified basal ganglia
94
What are drugs that cause hypocalcaemia
- Calcitonin – inhibition of bone resorption
- Bisphosphonates – inhibition of bone resorption
- Phosphate therapy – increased phosphate levels
95
Describe what can cause vitamin D deficiency leading to hypocalcaemia
- intestinal malabsorption - e.g. coeliac disease
- diet
- inadequate sunlight exposure
96
What investigations do you use in hypocalcaemia
- History and serum calcium - usually diagnostic
Other blood tests
- phosphate
- ALP
- U&Es
- PTH
- parathyroid Abs
- 25-hydroxyvitamin D
- magnesium
Other tests - X ray of metacarpals (pseudoparathyroidism)
97
What does primary and secondary hypoparathyroidism look like in blood
- calcium
- PTH
- phosphate
- ALP
- calcium = decreased
- PTH = decreased
- phosphate = increased or normal
- ALP = normal
98
What does psuedohypoparathyrodism look like in
- calcium
- PTH
- phosphate
- ALP
- calcium = decreased
- PTH = increased
- ALP = increased or normal
99
What is the difference between chronic and acute hypocalcaemia
- Chronic hypocalcaemia = <1.9mmol/L without symptoms
| - Acute hypocalcaemia = <1.9mmol/L with symptoms
100
how do you mange chronic hypocalcaemia
- calcium supplements
| - calcitriol
101
How do you manage acute hypocalcaemia
- IV calcium gluconate
| - alpha- calcidiol
102
What is the blood supply of the adrenal gland
- Superior, middle and inferior adrenal arteries anastomose underneath the capsule
- Medulla - supplied by long cortical arteries which drain blood from the cortex and therefore the blood may contain corticosteroids that influence that medulla's production of adrenaline
- cortex- supplied by short cortical arteries
103
What are the zones of the adrenal cortex
Zona glomerulosa – mineralocorticoids – aldosterone
- Na+ and K+ retention by the kidneys
Zona fasciculata – glucocorticoids – cortisol
- Glycogen, protein and fat breakdown into glucose; Suppression of immune system (prostaglandins)
Zona reticularis – androgens – dehydroepiandrosterone
- Sex steroids which have weak effect until peripheral conversion to testosterone and dihydrotestosterone
104
What causes secondary hyperaldosteronism
- due to increase renin from decreased renal perfusion e.g. renal artery stenosis, accelerated hypertension, diuretics, CCF, hepatic failure
105
what are the symptoms of Conns disease
- often asymptomatic
- hypokalaemia
- weakness
- cramps
- paraesthesiae
- polyuria
- polydipsia
- hypertension (not always)
106
What are the causes of hyperaldosteronism
- 2/3- Conn's syndrome: solitary aldosterone-producing adenoma
- 1/3- bilateral adenocortical hyperplasia
- rare causes - adrenal carcinoma, glucocorticoid-remediable aldosteronism (GRA)
107
What is the management of hyperaldosteronism
- Conn's - laparoscopic adrenalectomy + 4 weeks pre-op spironolactone - 25-100mg/24 hour PO (to decreases BP and increase potassium)
- hyperplasia - medically: spironolactone or amiloride
- GRA-1) dexamethasone 1mg/25hour PO for 4 weeks (normalities biochemistry but not always BP) OR 2) Spironolactone if blood pressure still raised
- adrenal carcinoma - surgery +/- post-operative adsrenolytic therapy with mitotane (prognosis is poor)
108
What is phaechromocytoma
- rare catecholamine-producing tumours arising fro sympathetic chromatin cells
109
What is the classic triad of phaechromocytoma
- episodic headache
- swelling
- tachycardia
blood pressure can be decreased, increased or normal
110
What are the features of phaechromocytoma
- Heart = tachycardia, palpitations/VT, dyspnoea, faints, angina, MI/LVF, cardiomyopathy
- CNS - headache, visual disorder, dizziness, tremor, numbness, fits, encephalopathy, Horner's syndrome, subarachnoid/CNS haemorrhage
- Psychological - anxiety, panic, hyperactivity, confusion, episodic psychosis
- Gut - D&V, abdominal pain over tumour site, mass, mesenteric vasoconstriction
- others - sweats/flushes, heat intolerance, pallor, fever, backache, haemopytsis
111
What does the ECG say in phaechromocytoma
- Signs of LVF
- raised ST segment
- VT
- Cardiogenic shock
112
What are the precipitating factors of phaechromocytoma
- straining
- exercise
- stress
- abdominal pressure
- surgery
- drugs (beta blockers, IV contrast agents, TCAs)
- sexual intercourse
- parturition
- defecation
- micturition
113
In what three cases should you think Conn's disease in hypertension
- Hypertension associated with hypokalaemia
- Refractory hypertension, eg despite ≥3 antihypertensive drugs
- Hypertension occurring <40yrs of age (especially in women)
114
Describe how Conn's syndrome leads to hypertension
- normally when BP or blood volume decreased, angiotensinogen is converted into angiotensin I (by renin in kidney)
- angiotensin I is converted to angiotensin II
- angiotensin II stimulates the release of CRH which stimulates ACTH release
- angiotensin II + ACTH + increase in potassium leads to aldosterone secretion
- in Conn's aldosterone secretion occurs pathologically in excess and its effects are:
- decrease in sodium and water excretion
- increase in potassium excretion
- renin suppression
This results in an increase in blood volume and pressure
115
Describe how renal artery stenosis leads to hypertension
- juxtaglomerular apparatus releases renin in reponse to lowered blood pressure in the afferent arterioles
116
describe how pheochromocytoma leads to hypertension
- Juxtaglomerular apparatus releases renin in reponse to sodium (excess from tumour)
