L5/6 - Adrenals

Question 1

What are the layers of the adrenal gland?

Answer 1

G- Glomerulosa (outside)
F- fasciculata
R - reticularis
Medulla in middle

Question 2

What the adrenal causes of hypertension?

Answer 2

Primary Hyperaldosteronism - problem with zona glomerulosa - may be due to adenoma, hyperplasia or rare genetic disorders

Phaeochromocytoma - Tumour of the adrenal medulla

Question 3

Whom to screen for primary hyperaldosteronism ?

Answer 3

Hypokalaemia
Resistant hypertension (3 drugs)
younger people

Question 4

What tests would you do for primary hyperaldosteronism ?

Answer 4

1 - Initial screening tests
suppressed renin 
Normal/High aldosterone 
Confirmatory tests - 
oral or IV sodium supression test 

Adrenal CT scan
Adrenal venous sampling
Metomidate PET CT

Question 5

Treatment for Primary Hyperaldosteronism

Answer 5

Unilateral adenoma - laparoscopic adrenalectomy
and sometimes medical treatment
Bilateral hyperplasia - medical treatment (aldosterone antagonist) spironolactone or eplerinone

Question 6

What are the products of the adrenal medulla?

Answer 6

catecholamines - dopamine, adrenaline 
noradrenaline - alpha 1/2
vasoconstriction, increased bp, pallor 
adrenaline - alpha 1 and beta 1+2 
vasoconstriction, vasodilation in muscles, increased HR, sweating

Question 7

How does phaeochromocytoma present?

Answer 7

Spells - headache, sweating, pallor, palpitation, anxiety
hypertension
family history

Question 8

What 3 genetic conditions are associated with phaechromocytoma?

Answer 8

NF1 - neurofibromatosis type 1 - Tumour under skin or deeper. Tumour which grows on the nerves
Also get axillary freckling
MEN2 - Multiple endocrine neoplasia type 2 - medullary carcinoma of thyroid
Von Hippel - Lindau syndrome - retinal hemangioglioblastoma

Question 9

How would you diagnose phaeochromocytoma?

Answer 9

24 hour urine - normetanephrines and metanephrines
Plasma - noradrenaline/adrenaline
metanephrines

Question 10

What other things can elevate the measured catecholamines?

Answer 10

L-DOPA
Amphetamine like drugs
Obstructive sleep apnoea
Labetalol

Question 11

Other tests

Answer 11

CT to identify it
Then MIBG - a nuclear medicine scan
Meta-iodobenzylguanidine

Question 12

Management for Pheo

Answer 12

Alpha blockers - phenoxybenzamine
doxazocin
BB - propanalol
Laparacopic adrenalectomy

Question 13

Post adrenalectomy care

Answer 13

consider genetic testing

annual metanephrines - plasma and 24 hour urines

Question 14

Why is calcium important?

Answer 14

exocytosis
- neurotransmitter secretion
hormone secretion
physical properties of bone

Question 15

How does hypocalcemia affect neurons?

Answer 15

destabilises them
so it is important to check - if someone has first fit - check their serum calcium as hypocalcemia can cause seizures
The reason hypocalcemia causes neuron excitation (contrary to the above logic) is because a decrease in extracellular calcium concentration increases the neuron membrane’s permeability to sodium and allows sodium to easily depolarize the neuron’s membrane and cause an action potential

Question 16

What physical signs are there are of hypocalcemia/

Answer 16

1) Trousseaus sign of latent tetany (carpopedal spasm) In a patient with hypocalcemia, carpal spasm may be elicited by occluding the brachial artery. To perform the maneuver, a blood pressure cuff is placed around the arm and inflated to a pressure greater than the systolic blood pressure and held in place for 3 minutes. If carpal spasm occurs, manifested as flexion at the wrist and metacarpophalangeal joints, extension of the distal interphalangeal and proximal interphalangeal joints, and adduction of the thumb and fingers, the sign is said to be positive and the patient likely has hypocalcemia

2 - Chvostek’s sign - low plasma calcium increases permeability of neuronal membranes to sodium. . If the plasma Ca2+ decreases to less than 50% of the normal value action potentials may be spontaneously generated, causing contraction of peripheral skeletal muscle

Question 17

What are consequences of hypercalcemia?

Answer 17

acute - thirst / polyuria/abdominal pain
chronic - constipation
osteoporosis
renal calculi

Question 18

How are calcium levels controlled within a narrow range?

Answer 18

Chief cells in the parathyroid glands make parathyroid hormone. results in increased calcium in serum. PTH release is determined by serum calcium concentration

Question 19

How does it know when the blood calcium is abnormal?

Answer 19

parathyroid chief cells have calcium sensing receptors
a part of GPCR family.
The calcium-sensing receptor (CaSR) is sensitive to an increase in serum calcium, and stimulates the uptake of calcium by the parathyroid chief cell. This mechanism is critically important, as it describes a physiological feed-back loop by which parathyroid hormone secretion is down-regulated in response to a restoration of serum calcium.

Question 20

How does magnesium affect PTH?

Answer 20

Low magnesium prevents PTH release?

Question 21

How does PTH work?

Answer 21

Binds PTH type 1 receptor which is a GPCR. activation of adenylyl cyclase. PTH activates the receptor by changing its shape

Question 22

Where are PTH receptors?

Answer 22

bone and kidney

Question 23

PTH and Bone

Answer 23

The first action is to increase renal calcium resorption and phosphate excretion. In the kidney, PTH blocks reabsorption of phosphate in the proximal tubule while promoting calcium reabsorption in the ascending loop of Henle, distal tubule, and collecting tubule. Calcium also may exert a direct effect on renal resorption.
PTH promotes absorption of calcium from the bone in 2 ways.
a. The rapid phase brings about a rise in serum calcium within minutes and appears to occur at the level of the osteoblasts and osteocytes. Although it may seem counterintuitive that the cells that promote deposition of bone are involved in resorption, these cells form an interconnected network known as the osteocytic membrane overlying the bone matrix, but with a small layer of interposed fluid termed bone fluid. When PTH binds to receptors on these cells, the osteocytic membrane pumps calcium ions from the bone fluid into the extracellular fluid.

Question 24

How is calcium released from bone?

Answer 24

PTH stimulates osteoblasts - rank ligand produced by osteoblasts- rank - osteoclast activation -
excess RankL drives bone destruction
Osteoclasts break down bone. - bone resorption

Question 25

Action of PTH on kidneys

Answer 25

Rapid calcium reabsorption in loop of henle, dt and cd.
reduced phosphate reabsorption in PT.
PTH important for Vitamin D. which is needed for calcium absorption
Kidneys regulate production of 1,25 (OH)2D. PTH stimulates and FGF23 inhibits the production.
In turn, 1,25(OH)2D inhibits PTH production and secretion of the PTH gland and stimulates FGF23 production from bone.
OSTEOCYTES MAKE FGF23 WHICH MAKES YOU PEE OUT LOADS OF PHOSPHATE - RENAL PHOSPHATE EXCRETION

Question 26

problems with calcium metabolism

Answer 26

Primary hyperparathyroidism

diagnosis: serum calcium increased, serum phosphate reduced and PTH increased

Question 27

What are complications of hyperparathyroidism?

Answer 27

osteoporosis

bone cysts

Question 28

Complication of hypercalcemia

Answer 28

renal stones

Question 29

Levels in hypoparathyroidism

Answer 29

serum calcium low

PTH can be low or normal

Question 30

What are causes of hypoparathyroidism?

Answer 30

iatrogenic - thyroidectomy, radical neck surgery
autoimmune
hypomagnesaemia
genetic mutations

Question 31

What are causes of secondary hyperparathyroidism?

Answer 31

low serum calcium and HIGH PTH
low serum 25 OH vit D
lack of sun exposure/GI problems
renal failure

Question 32

What is rickets

Answer 32

A softening of the bones in children potentially leading to fractures and deformity.