Clinical endocrinology - Gunn

Question 1

Differential diagnosis for fatigue and weight loss

Answer 1

Psychological (major depression) 
Metabolic (e.g. diabetes mellitus) 
Chronic infection (HIV, TB, post viral) 
Chronic gut or heart or renal disease 
Cancer 
Other endocrine (Additions disease)

Question 2

Blood sugar levels

Fasting and post prandial

Answer 2

Fasting

• <5.6 mammal/L is normal (100mg/dl)
• 5.6 to 6.9 = impaired glucose tolerance
• > 7 on two = diabetes

postprandial
< 7.8 mol/L is normal
7.8 to 11 impaired glucose tolerance
>11 = diabetes

Question 3

WHO definition of TIDM

Answer 3

Fasting glucose > 7mmol/L 
OR 
post prandial glucose > 11.1mmol/l 
OR 
HbA1c > 48mmol/mol
AND 
Insulin deficiency 
Clinical signs of an insulin deficiency syndrome 
(polyuria, polydipsia, weightless, ketoacidosis)

Question 4

Why was the patient thirsty?

Answer 4

plasma glucose over the tubular maxima (~>10mmol/L) therefore excess glucose lost in urine
Osmotic diuresis: high water loss, tending to iso-osmotic. Mechanisms: reduced efficiency of LoH
- Increased flow — reduced concentration
Osmotic diuresis from unreabsorbed glucose and ketone salts retaining water in DCT/CD
Volume loss from loss of ketone salts (i.e Na+ and Ketone)
Non specific mechanisms
- nausea, general unwell –> water intake decreased
Net dehydration, mainly pure water loss
- AVP release: aquaporins open –> retain maximal water
- ALDO release: retain max amount of salt

Question 5

What are Kussmauls respirations

Answer 5

respiratory compensations for metabolic acidosis, leading to hypocapnia
She had metabolic acidosis pH 7.2

Question 6

Explain patients serum Na+ of 132 mol/L (normal 135-146 mol/L)

Answer 6

Effective osmolality = (2x measured serum sodium) + serum glucose

Question 7

glucose corrected serum sodium

Answer 7

measured serum sodium + ([glucose - 5.5] x 0.288)
132+(29.5-5.5)x0.288 = 139 mol/L
She is not hyponatremic, merely diluted by hyperglycaemia (i.e water shift out of cells –> ECF)
= pseudoyponatremia

Question 8

Why was she initially passing little urine, but after partial rehydration she began passing a large volume of urine in spite of clinical dehydration

Answer 8

Volume contraction + intense sympathetic nervous system activity, angiotensin II –> reduced RBF and GFR
she is in a form of pre renal failure.
rehydration –> restoration of GFR,

Question 9

Serum K+ was 5.1 mol/L at time of admission by following initial treatment with IV fluids serum K+ was 2.8mmol/L

Answer 9

Short version: Whole body potassium deletion due to ketoacidosis
- masked acidosis, insulin deficiency etc
Treatment –> rapid shift of K into cells
- replacement of insulin
- fall of osmolarity
- correction of acidosis

Question 10

What are some of the forces displacing K from cells?

Answer 10

Lack of insulin –> dec Na/K ATPase –> K out of cells
Acidosis decNa/K ATPase
Milder effect on sK with Ketoacidosis than some forms of metabolic acidosis
- because developes relatively progressively
Ketoacids have less effect

Once in plasma is then excreted in the urine
ALDO, due to volume contraction + high normal K+
K > 4.2mmol/L high normal
Polyuria due to osmotic diuresis
- greater dilution of urine [K] –> better gradient for excretion
Potential inhibitor: effect of acidosis on Na/K ATP-a
- again ketoacidosis less effect on kidney or just counter balanced by above effect leading to net effect to increase excretion

Question 11

Multiple forces displacing insulin from cells?

Answer 11

Multiple forces displacing K from cells
- Lack of insulin –> dec Na/K ATPase –> K out of cells
Acidosis: dec Na/K ATPase
milder effect on sK with ketoacidosis than some forms of metabolic acidosis

Insulin tends to shift potassium form the ECF back into cells, a lack of insulin allows then back out

Question 12

Evolving diabetes and DKA lead to progressive whole body loss of?

Answer 12

intracellular K

Question 13

Why her serum glucose fell dramatically?

Answer 13

1. Dilution: in part her serum glucose was high because of dehydration. 30ml/Kg bolus of 0.9% saline diluted the glucose
2. Diuresis after fluid loading: she had continued osmotic diuresis. If urine is isosmotic, with maximal reabsorption of Na by ALDO then she could have lost unto 300mmol/L of glucose in urine.
3. We gave insulin –> activation of GLUT4 in fat / muscle, glycogen synthetase and pyruvate dehydrogenase
   so glucose uptake and incorporation
   so turn off gluconeogenesis / release

Question 14

What happened to her mental status after the start of treatment

Answer 14

She has developed a hyper osmotic state over several days, allowing normalisation

Question 15

Cerebral oedema in treatment of this condition

Answer 15

Rare complication
Aetiology unclear: severe DKA + Tx
Presumptively
- intracellular hyperosmolarity has developed
- rapid reduction in ECF osmolarity during treatment –> brain swelling
Slow correction seems to be safer

Question 16

Why would a DI patients have an initial NORMAL serum sodium?

Answer 16

sNa = 142 mol/L Because she has access to water and intact thirst

Question 17

Other reasons why the patient could be drinking too much water?

Answer 17

Excessive psychological drinking

Question 18

What is the significance of the increase in early morning blood osmolarity

Answer 18

excessive loss of free water overnight

Question 19

Why is the early morning urine osmolarity inadequately normal? 350mosml/L?

Answer 19

Failure to concentrate despite abnormally high sNa/ plasma osmolarity

Question 20

Why did the urine osmolarity rise after giving desmopressin?

Answer 20

Desmopressin = log acting ADH
V2 –> insertion of AQP in CD = max concentration of urine
Thus she has central DI

Question 21

If the urine osmolarity had not increased that would suggest?

Answer 21

Renal resistance to ADH
aka nephrogenic diabetes insipidus
- Acquired forms of NDI are more common in adults
- Congential causes are more common in children, most have X linked pattern of inheritance
The affected male patients do not concentrate their urine, even after admin of exogenous vasopressin
thus can diuresis for 20L per day and may only sleep for 1-2 hours at a time

Question 22

What are the types of Addison’s diseases?

Answer 22

primary: adrenal insufficiency (note aldosterone secretion is not dependant on ACTH. however patients with secondary additions disease can present with hypovolemia/ hypotension + high sK during severe stress e.g. acute gastroenteritis, major trauma etc.
Central: secondary adrenal insufficiency due to a pituitary problem

Question 23

Addison’s disease why does the patient have a low serum sodium

Answer 23

Na+ concentration depends on ADH response
Volume receptors tonically inhibit ADH release
- sensitive to 5-10% cane in volume
- much less than osmoreceptors (1-2% change)
His BP is low stimulating ADH release
- Decrease in blood volume –> set points shifts to lower osmolality and slope is steeper
i.e kidney conserves water despite reduction in osmolality

Question 24

Why is K+ high?

Answer 24

Insufficient levels of aldosterone (+ cortisol)

Question 25

Why is his BP low

Answer 25

Volume contraction from low aldosterone –> loss of whole body NaCl (Usually volume contraction not present of mild in central additions except during severe stress)
Lack of cortisol
- cortisol interacts with B1 adrenergic stimulus to increase cardiac tone
- Cortisol interacts with RAS+ B1 stimulation to maintain peripheral tone

Question 26

Why is the patient tanned?

Answer 26

ACTH stimulates melatonin
This means high ACTH not seen in central additions: key is areas not exposed to sun e.g. skin creases (fake tan watch out) buccal mucosa.