MET3 Revision: Endocrine II

Question 2

State the 4 grades of hypertensive retinopathy

Answer 2

 Grade 1 – silver (copper) wiring
 Grade 2 – arteriovenous nipping
 Grade 3 – flame shaped haemorrhages + exudates
 Grade 4 - papilloedema

Question 3

Name a cardiac cause of secondary hypertension [1]

Answer 3

Coarctation of the aorta(differential BP between upper and lower limb and arms; radio-radial delay)

Question 4

Name three renal causes of secondary hypertension [3]

Answer 4

• CKD
• Glomerulonephritis
• Renovasculardisease

Question 5

Name 4 endocrine causes of secondary hypertension [4]

Answer 5

• Conns
• Cushings
• Phaeochromocytoma
• Acromegaly

Question 6

Conn’s syndrome refers to an adrenal adenoma producing too much aldosterone.

What are the two options that this could be caused by? [2]

Which is more likely? [2]

Answer 6

Solitary aldosterone producing adenoma
* 2/3rds

Bilateral adrenocortical hyperplasia
* 1/3rd

Question 7

You suspect a ptx with Conns syndrome; how would you expect their blood gas to appear after investigation? [1]

Answer 7

Hypokalaemic alkalosis (XS aldosterone causes increased K+ secretion and Na+ absorption)

Question 8

You suspect a patient has Conn’s syndrome due their refractory BP.

Name a differential diagnosis that is more common cause of this [1]

Answer 8

Renal artery stenosis

Question 9

Apart from investigating electrolytes, what further tests (and results) would you conduct for a ptx suspected to have hyperaldosteronism? [4]

Answer 9

Hyperaldosteronism investigations:
- Plasma renin: suppressed
- Elevated serum aldosterone
(these tests are conducted together: paired renin/aldosterone level)
- CT adrenals
- Adrenal vein sampling to differentiate unilateral from bilateral adrenal disease

Question 10

What are clinical presentations of Conn’s syndrome? [6]

Answer 10

• Often asymptomatic
• cramps
• muscle weakness
• hypotonia
• reduced reflexes
• Hypertension (often have resistant HTN or severe HTN)
• 40-60 years old
• Hypokalaemic (but NOT always present, so can’t rely on this for diagnosis)

often the signs are due to hypokalaemia

Question 11

What is the management of unilateral adrenal adenoma? [1]
What is the management of bilateral adrenal hyperplasia? [2]

Answer 11

Unilateral adrenal adenoma: Surgery (laparoscopic adrenalectomy)

Bilateral adrenal hyperplasia: aldosterone antagonist
- eplerenone
- spironolactone

Question 12

What is the 10% rule for phaeochromocytoma? [4]

Answer 12

 10% extra adrenal
 10% malignant
 10% familial (endocrine neoplasia syndromes)
 10% bilateral

Question 13

Presentation of phaeochromocytomas? [5]

Answer 13

Classic triad:
* Tachycardia
* Sweating
* Episodic headache

Others:
* Tremor
* Anxiety
* Palpitations
* Hypertension
* Tachycardia

Question 14

*

Why does prescribing beta blockers worsen symptoms for patients with phaeochromocytoma? [2]

Answer 14

Inhibits B2 receptor action (vasodilatation);

Causes unparalleled action of A1 and A2 receptors (vasoconstriction)

Can cause severe hypertensive crisis

Question 15

Which drugs would you prescribe for symptoms of phaeochromocytoma? [2]

What is an alternative management? [1]

Answer 15

Always give alpha blockers first (otherwise can cause hypertensive crisis; then beta blockers)

Alpha blockers:
 Doxazosin
 Phenoxybenzamine

Beta blockers (if heart disease or tachycardic)
 Propranolol
 Atenolol

and / or

Surgical resection of the lesion
(Patients have their symptoms controlled medically before surgery to reduce the anaesthesia and surgery risks)

Question 16

Initial tests for diagnosing phaeochromocytoma include? [4]

Answer 16

• Elevated plasma free metanephrines (breakdown products of the catecholamines epinephrine (adrenaline) and norepinephrine)
• Elevated 24-hour urine catecholamines (not as accurate as measuring metanephrines)
• Image adrenals (CT/MRI)
• MIBG (radionucleotide scan of Iodine-123)

Question 17

Describe the treatment options for acromegaly [3]

Answer 17

• 1st line: trans-sphenoidal surgery

Medical management of acromegaly:

• Somatostatin analogues: Octreotide
• Growth hormone receptor antagonist:: Pegvisomont

Question 18

What is the MoA of Pegvisomont? [1]

Answer 18

Used to treat acromegaly: GH Receptor antagonist

Question 19

What is the role of calcitonin? [2]
Where is it produced? [1]

Answer 19

Lowers Ca2+ & P levels by:
- Inhibits Ca2+ absorption by intestines
- Inhibits Ca2+ reabsorption in kidney
- Promotes osteoblasts, inhibits osteoclasts

Secreted by C cells of thyroid

Question 20

Hypercalcaemia has what effect on urine and thirst? [1]

Answer 20

Causes polyuria and polydipsia

Question 21

Give three differential diagnoses for polyuria and polydipsia [3]

Answer 21

DM
Diabetes insipidus
Hypercalcaemia

Question 22

How should you manage acute hypercalcaemia? [1]
What drug should you prescribe if Ca2+ remains elevated? [1]

Answer 22

1. Give IV saline alone
2. If Ca still high - give bisphosphinates; pamidronate: prevent bone resorption by inhibiting osteoclast activity

Question 23

Describe dosing of pamidronate for acute hypercalcaemia [1]

Name 2 SEs [2]

Answer 23

Single dose of (4mg) will will normalise serum Ca2+ levels with a week

SEs:
- Bone pain
- Decresed PO4-
- Myalgia
- N & V
- Ca2+ decreasing

Question 24

Describe the causes of [3]

Primary hyperparathyroidism
Secondary hyperparathyroidism
Tertiary hyperparathyroidism

Answer 24

Primary hyperparathyroidism:
- is caused by uncontrolled parathyroid hormone production by a tumour of the parathyroid glands
- this leads to a raised blood calcium (hypercalcaemia)

Secondary hyperparathyroidism:
- is where insufficient vitamin D or chronic kidney disease reduces calcium absorption from the intestines, kidneys and bones.
- this result in low blood calcium (hypocalcaemia).
- The parathyroid glands react to the low serum calcium by excreting more parathyroid hormone.
- The serum calcium level will be low or normal, but the parathyroid hormone will be high.

Tertiary hyperparathyroidism:
- when secondary hyperparathyroidism continues for an extended period, after which the underlying cause is treated
- hyperplasia (growth) of the parathyroid glands occurs as they adapt to producing a higher baseline level of parathyroid hormone
- Then, when the underlying cause of the secondary hyperparathyroidism is treated, the baseline parathyroid hormone production remains inappropriately high.
- In the absence of the previous pathology, this high parathyroid hormone level leads to the inappropriately high absorption of calcium in the intestines, kidneys and bones, causing hypercalcaemia. Treatment is surgically removing part of the parathyroid tissue to return the parathyroid hormone to an appropriate level.

Question 25

State the most likely cause of: Primary hyperparathyroidism [2] Secondary hyperparathyroidism [2] Tertiary hyperparathyroidism [1]

Answer 25

**Primary hyperparathyroidism** * Solitary adenoma (80%) * Hyperplasia (20%) **Secondary hyperparathyroidism** * Vit D deficiency (reduced intake) * CKD - difficulty making Vit D **Tertiary hyperparathyroidism** - Secondary hyperparathyroidism

Question 26

If you investigate raised hypercalcaemia and find PTH to be undetactable, what would this indicate? [1] Give three causes of the above [3]

Answer 26

**Malignancy**: PTH related Peptide (PTHrP) causes the increased Ca2+ levels, but itself is undetectable E.g. **squamous cell lung cancers; breast, renal cell carcinomas**

Question 27

How would you investigate for hypercalcaemia if PTH is high? [1] How would you investigate for hypercalcaemia if PTH is low? [1]

Answer 27

**PTH high: indicates hyperparathyroidism** - USS - SestaMibi Scan - Parathyroid venous sampling **PTH low: indicates cancer:** - test for PTH related Peptide (PTHrP) - but can't measure this - so do local body signs of cancer and further tests

Question 28

Give differential diagnosis of primary hyperparathyroidism [3]

Answer 28

Thiazide like diuretics [1] Lithium [1] Tertiary hyperparathyroidism [1]

Question 29

What blood tests would you use to investigate primary hyperparathyroidism

Answer 29

* Ca2+ and PTH raised * ALP raised (due to bone activity) *

Question 30

Describe a radiographical sign of hyperparathyroidism [1]

Answer 30

**Pepper pot skull**: extensive resorption bone in the skull in combination with cystic areas of osteopenia are termed pepper pot skull.

Question 31

What are clinical presentations of Conn's syndrome? [4]

Answer 31

- Often **asymptomatic** - **Hypertension**: often have **drug resistant or severe HTN** - 40-60 years old - **Hypokalaemic** (but NOT always present) - therefore signs of hypokalameia

Question 32

How do you treat hyperparathyroidism? - Surgically? [1] - Therapeutically? [1]

Answer 32

 **Parathyroidectomy**  **Cinacalcet** directly lowers parathyroid hormone levels by increasing the sensitivity of the calcium sensing receptors to activation by extracellular calcium, resulting in the inhibition of PTH secretion. Indicated in patients with: - **Chronic renal failure** - **Tertiary hyperparathyroidism**

Question 33

When is cinacalcet indicated for treatment of hypeparathyroidism? [2] What is the MoA? [1]

Answer 33

- Used for patients with **chronic renal failure and tertiary hyperparathyroidism** - Increases the sensitivity of parathyroid cells to Ca2+ thereby causing less PTH secretion

Question 34

Acute severe hypercalcaemia is a MEDICAL EMERGENCY. State how you would treat a ptx suffering from acute severe hypercalcaemia [4]

Answer 34

* Rehydrate with **IV 0.9% saline** fluids - to prevent stones * **Furosemide**: loop diuretic that increases Ca2+ excretion * Give bisphosphonates (to prevent bone resorption by inhibiting osteoclasts) after rehydration **e.g. IV PAMIDRONATE** * Measure **serum U&E’s daily and serum Ca2+ 48hrs after initial treatment** * Can give glucocorticoid steroids e.g. **ORAL PREDNISOLONE** in myeloma, sarcoidosis and vitamin D excess

Question 35

What is the name of this sign? [1] When does it occur? [1] What does it indicate? [1]

Answer 35

**Trousseau sign**: hypocalcemia The hand adopts a characteristic posture when the sphygmomanometer cuff is inflated above the systolic blood pressure within 3 minutes.

Question 36

What is the name of this sign? [1] How do you illicit this sign? [1] What does it indicate? [1]

Answer 36

**Chvostek's Sign**: - indiactes **hypocalcaemia** - This clinical sign refers to a twitch of the facial muscles that occurs when gently tapping an individual's cheek, in front of the ea

Question 37

How do you treat ptx with hypocalcaemia: With < 1.9 Ca2+, no symptoms? [2] With < 1.9 Ca2+, symptoms? [2]

Answer 37

 < 1.9 with no symptoms -  **Oral calcium supplements** -  If due to severe vitamin D def, treat with **high dose vit D** (Calcitriol)  < 1.9 with symptoms -  **IV calcium gluconate**

Question 38

State 5 causes of hypocalcaemia [5]

Answer 38

 Thyroid / parathyroidectomy  Severe vitamin D deficiency  Magnesium deficiency (PPI induced - PPIs needed for PTH to work)  Pancreatitis  Cytotoxics

Question 39

What pathology is this a sign of? [1] Explain

Answer 39

**Pseudohypoparathyroidism** is a rare genetic metabolic bone disease caused by a defect in the GNAS1 protein that leads to a decreased response to PTH. Patients present with **characteristic findings of short 4th and 5th metacarpals, round facies, short stature, and symptoms of hypocalcemia**.

Question 40

How does renal artery stenosis cause HTN? [2]

Answer 40

- **Atherosclerosis** or fibromuscular dysplasia most causes narrowing of the renal arteries - The chronic ischemia produced by the obstruction of renal blood flow leads to adaptive changes in the kidney which include the **formation of collateral blood vessels and secretion of renin by juxtaglomerular apparatus**

Question 41

What are the radiological investigations of suspected Conn's syndrome and phaeochromocytoma? [1]

Answer 41

Use MIBG scan: Iodine-123

Question 42

[] is used to diagnose patients with primary hyperaldosteronism (Conn's syndrome) when the adrenal CT scan does not show a tumor

Answer 42

**Adrenal vein sampling** is used in patients with primary hyperaldosteronism (Conn's syndrome) when the adrenal CT scan does not show a tumor

Question 43

State the overarching causes of hypocalcaemia [8]

Answer 43

- Secondary to increased serum phosphate levels: CKD - Severe vitamin D deficiency - Reduced PTH production: **Primary hypoparathyroidism** & **Secondary hypoparathyroidism** - **Radiation** - **Hypomagnesaemia** - Mg is required for PTH secretion - **Pseudohypoparathyroidism**: failure of target cell response to PTH due to owing to a mutation in the Gs alpha-protein (GNAS1), which is coupled to the PTH receptor - **Pseudopseudohypoparathyroidism**: Same phenotypic defects as pseudohypoparathyroidism e.g. short stature; but without any abnormalities of Ca2+ metabolism - Drugs: **Calcitonin** - decreases plasma Ca2+ and phosphate; **Bisphosphonates** - reduce osteoclast activity resulting in reduced Ca2+ - **ACUTE PANCREATITIS**

Question 44

Describe the causes of primary and secondary hypoparathyroidism [2]

Answer 44

**Primary hypoparathyroidism**: - caused by **autoimmune** DiGeorge syndrome (Congenital familial condition in which the parathyroid glands fail to develop; - **idiopathic hypoparathyroidism** **Secondary hypoparathyroidism** - After **parathyroidectomy** or **thyroidectomy** surgery. most common cause)

Question 45

Clinical presentation of hypocalcaemia? [6]

Answer 45

* Increase **excitability** of **muscles** and **nerves** * **Parathesiae** (numbness and tingling) around the mouth and in the extremities, followed by **cramps, tetany** * **Convulsions** and death if untreated * **Chvostek**’s sign: (tapping over the facial nerve in the region of the parotid gland causes twitching of the IPSILATERAL facial muscles * **Trousseau**’s sign: carpopedal spasm induced by inflation of sphygmomanometer cuff to a level above systolic blood pressure * **papilloedema** and a **prolonged QT** on ECG (severe hypocalcaemia)

Question 46

How would differentiate unilateral from bilateral adrenal disease? [1]

Answer 46

Adrenal vein sampling