Endocrinology:Endocrine Hypertension and Calcium Disorders

Question 1

State the 4 grades of hypertensive retinopathy

Answer 1

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

Question 2

Name a cardiac cause of secondary hypertension [1]

Answer 2

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

Question 3

Name three renal causes of secondary hypertension [3]

Answer 3

• CKD
• Glomerulonephritis
• Renovasculardisease

Question 4

Name 4 endocrine causes of secondary hypertension [4]

Answer 4

• Conns
• Cushings
• Phaeochromocytoma
• Acromegaly

Question 5

What grade of retinopathy is depicted? [1]

Answer 5

Grade 4

Question 6

Label A

Answer 6

Optic disc swelling

Question 7

• 35y/0 man admitted with headaches
• c/o muscle weakness, frequent urination
• O/E BP210/100mmHg
• Grade 4 retinopathy

Answer 7

Conn’s syndrome (Hyperaldosteronism - indicated by low K and hypertension; not Cushings as you would expect other clinical signs)

Question 8

Conn’s syndrome refers to an [] producing too much aldosterone.

Answer 8

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

Question 9

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 9

Solitary aldosterone producing adenoma
* 2/3rds

Bilateral adrenocortical hyperplasia
* 1/3rd

Question 10

What is the key presenting feature of hyperaldosteronism? [1]

Answer 10

Hyperaldosteronism may be present in 5-10% of patients with hypertension.

Hypertension is the key presenting feature, and many patients are otherwise asymptomatic. It may cause non-specific symptoms such as headaches, muscle weakness and fatigue.

Question 11

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

Answer 11

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

Question 12

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 12

Renal artery stenosis

Question 13

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

Answer 13

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 14

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

Answer 14

• 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 15

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

Answer 15

Unilateral adrenal adenoma: Surgery (laparoscopic adrenalectomy)

Bilateral adrenal hyperplasia: aldosterone antagonist
- eplerenone
- spironolactone

Question 16

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

Answer 16

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

Question 17

Presentation of phaeochromocytomas? [5]

Answer 17

Classic triad:
* Tachycardia
* Sweating
* Episodic headache

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

Question 18

*

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

Answer 18

Inhibits B2 receptor action (vasodilatation);

Causes unparalleled action of A1 and A2 receptors (vasoconstriction)

Can cause severe hypertensive crisis

Question 19

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

What is an alternative management? [1]

Answer 19

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 20

Initial tests for diagnosing phaeochromocytoma include? [4]

Answer 20

• 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 21

Describe the treatment options for acromegaly [3]

Answer 21

• 1st line: trans-sphenoidal surgery

Medical management of acromegaly:

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

Question 22

What is the MoA of Pegvisomont? [1]

Answer 22

Used to treat acromegaly: GH Receptor antagonist

Question 23

Serum Ca2+ is mainly controlled by which hormones? [2]

Answer 23

parathyroid hormone (PTH) and vitamin D

Question 24

PTH has many actions - all serving to increase plasma Ca2+ levels.

State what they are [5]

Answer 24

• Increasing osteoclastic resorption of bone - occurs rapidly
• Increasing intestinal absorption of Ca2+ - slow response
• Activation of 1,25-dihydroxyvitamin D (calcitriol) in the kidney
• Increasing renal tubular reabsorption of Ca2+
• Increasing excretion of phosphate

Question 25

What is the name for the active form of vitamin D? [1] Name 3 causes of active vitamin D secretion [3]

Answer 25

Calcitriol: - Low plasma Ca2+ - Low plasma phosphate - PTH

Question 26

State 4 roles of calcitriol [4] (active form of vitamin D)

Answer 26

- Increased Ca2+ and phosphate absorption in the gut - Increased Ca2+ and phosphate reabsorption in the kidney’s - Inhibits PTH release - negative feedback - Enhanced bone turnover by increasing numbers of osteoclasts

Question 27

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

Answer 27

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 28

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

Answer 28

Causes **polyuria** and **polydipsia**

Question 29

Give three differential diagnoses for polyuria and polydipsia [3]

Answer 29

DM Diabetes insipidus Hypercalcaemia

Question 30

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

Answer 30

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

Question 31

Describe dosing of pamidronate for acute hypercalcaemia [1] Name 2 SEs [2]

Answer 31

Single dose of (4mg) will will normalise serum Ca2+ levels with a week SEs: - Bone pain - Decresed PO4- - Myalgia - N & V - Ca2+ decreasing

Question 32

Describe the causes of [3] Primary hyperparathyroidism Secondary hyperparathyroidism Tertiary hyperparathyroidism

Answer 32

**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 33

Answer 33

Question 34

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

Answer 34

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

Question 35

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

Answer 35

**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 36

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

Answer 36

**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 37

Give differential diagnosis of primary hyperparathyroidism [3]

Answer 37

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

Question 38

What blood tests would you use to investigate primary hyperparathyroidism [2]

Answer 38

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

Question 39

Describe a radiographical sign of hyperparathyroidism [1]

Answer 39

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

Question 40

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

Answer 40

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

Question 41

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

Answer 41

 **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 42

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

Answer 42

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

Question 43

Which drug class should you avoid with patients suffering from primary hyperparathyroidism causing hypercalcaemia? [1]

Answer 43

Avoid **THIAZIDE DIURETICS** and high Ca2+ and vitamin D intake

Question 44

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

Answer 44

* 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 45

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

Answer 45

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

Question 46

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

Answer 46

**Chvostek's Sign**: - 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 47

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

Answer 47

 < 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 48

State 5 causes of hypocalcaemia [5]

Answer 48

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

Question 49

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

Answer 49

**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 50

How does renal artery stenosis cause HTN? [2]

Answer 50

- **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 51

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

Answer 51

Use MIBG scan: Iodine-123

Question 52

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

Answer 52

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

Question 53

Hypercalcaemia is RARELY the FIRST PRESENTING SYMPTOM of malignancy Therefore, hypercalcaemia in an otherwise well outpatient is most likely to be due to []

Answer 53

hypercalcaemia in an otherwise well outpatient is most likely to be due to **primary** **hyperparathyroidism**

Question 54

Explain why CKD is the most common cause of hypocalcaemia [2]

Answer 54

Results from **inadequate production of active vitamin D and renal phosphate retention** Resulting in micro-precipitation of phosphate in the tissues

Question 55

State the overarching causes of hypocalcaemia [8]

Answer 55

- 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 56

Describe the causes of primary and secondary hypoparathyroidism [2]

Answer 56

**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 57

Clinical presentation of hypocalcaemia? [6]

Answer 57

* 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 58

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

Answer 58

Adrenal vein sampling