Endocrinology

Question 1

what is Cushing’s syndrome

Answer 1

a syndrome caused by prolonged exposure to an excess of glucocorticoids

Question 2

what is cushing’s disease

Answer 2

Cushing’s disease refers to cases caused by a pituitary adenoma. These are responsible for the majority of endogenous cases

Question 3

what is cortisol secretion controlled by

Answer 3

Cortisol secretion is controlled by the hypothalamus-pituitary-adrenal axis

Question 4

where is cortisol released from

Answer 4

adrenal cortez

Question 5

what is the pattern of its concentration

Answer 5

diurnal variation

It reaches a zenith (highest point) at around 8 am and a nadir (lowest point) at around midnight to 1 am.

Question 6

List 4 causes of Cushing’s syndrome

Answer 6

ACTH dependent:
- Cushing’s disease: pituitary adenoma releasing excess ACTH

ectopic ACTH producing tumour

ACTH independent

• therapeutic corticosteroid medication
• adrenal tumour

Question 7

What hormones are inivolved in cortisol homeostasis

Answer 7

Corticotroponin-releasing hormone (CRH)

adrenocortocotropic hormone (ACTH)

cortisol

Question 8

symptoms of cushing’s syndrome

Answer 8

Tiredness
Depression
Weight gain
Easy bruising
Amenorrhoea
Reduced libido
Striae

Question 9

signs of cushing’s disease

Answer 9

Acne
Moon facies
Plethora
Buffalo hump
Hypertension
Proximal muscle weakness
Hyperpigmentation (in ACTH dependent causes)

Question 10

investigations in Cushing’s Syndrome

Answer 10

24 hour urinary cortisol (multiple collections; 3-4x normal = highly suggestive of Cushing’s syndrome

midnight (salivary) cortisol: demonstrate loss of normal circadian pattern

1mg overnight dexamethasone suppression test: demonstrates loss of normal negative feedback on pituitary gland and hypothalamus

Question 11

what are risks of untreated Cushing’s syndrome

Answer 11

Untreated Cushing’s syndrome can be lethal with death from cardiac, thromboembolic or infective complications.

Question 12

management of Cushing’s syndrome

Answer 12

definitive treatment: surgical resection

Question 13

what is SIADH

Answer 13

The syndrome of inappropriate anti-diuretic hormone (SIADH) results from excess ADH secretion.

Question 14

what is the relationship between osmolality and ADH

Answer 14

ADH release is governed by the plasma osmolality

Question 15

What does SIADH result in

Answer 15

This results in a low plasma osmolality and a euvolaemic hyponatraemia.

Question 16

What part of the kidney does ADH act on

Answer 16

ADH acts on the distal convoluted tubule and collecting duct to increase water reabsorption independent of sodium. ADH stimulates the insertion of aquaporin-2 channels onto the luminal membrane, allowing the free entry of water. ADH also causes vasoconstriction of arterioles.

Question 17

CNS causes of SIADH

Answer 17

Stroke
Subarachnoid haemorrhage
Trauma
Psychosis

Question 18

neoplastic causes of SIADH

Answer 18

Small cell lung cancer (paraneoplastic syndrome)
Other lung cancers (less commonly)
Neuroblastoma

Question 19

infective causes of SIADH

Answer 19

pneumonia

HIV

Question 20

drugs that cause SIADH

Answer 20

Carbamazepine
Cyclophosphamide
Selective serotonin reuptake inhibitors (SSRIs)
MDMA (Ecstasy)

Question 21

hormonal causes of SIADH

Answer 21

Hypothyroidism

Hypopituitarism

Question 22

iatrogenic causes of SIADH

Answer 22

Common following many procedures

Particular risk in transsphenoidal pituitary surgery

Question 23

clinical features of SIADH

Answer 23

• similar to hyponatraemia
  symptoms: headache, confusion, lethargy, anorexia
  signs: seizuresm reduced GCS, coma, myoclonus, ataxia, hyporeflexia, asterixis

Question 24

what is the risk of rapid correction of hyponatraemia

Answer 24

osmotic demyelination syndrome

aka cerebral pontine myelinolysis

Question 25

management of SIADH

Answer 25

- fluid restriction - vaptans severe: ICU, hypertonic saline, furosemide

Question 26

what is the typical starting dose for metformin what is the maximum dose of metformin

Answer 26

500mg daily | 2g daily

Question 27

side effects of metformin

Answer 27

commonest: GI upset (nausea, abdominal pain, diarrhoea) rare: lactic acidosis

Question 28

what is the mechanism of metformin

Answer 28

Metformin reduces hepatic glucose production and acts systemically to increase glucose uptake.

Question 29

what are contraindications of metformin

Answer 29

acute metabolic acidosis e.g. DKA: stop treatment eGFR<30

Question 30

criteria for HHS

Answer 30

hypovolaemia severe hyperglycaemia >30 mild or absent ketones high osmolality > 320

Question 31

complications of HHS

Answer 31

``` AKI electrolyte disturbance hypotension coma VTE ```

Question 32

precipitants of HHS

Answer 32

``` Infection High-dose steroids Myocardial infarction Vomiting Stroke Poor treatment concordance ```

Question 33

signs of HHS

Answer 33

``` Dehydration (dry mucous membranes, sunken eyes, reduced capillary refill, decreased skin turgor) Hypotension Decreased urine output Decreased conscious level Coma Focal neurology signs Features of the precipitating cause ```

Question 34

symptoms of HHS

Answer 34

``` Polydipsia Polyuria Nausea Vomiting Muscle cramps Weakness Altered mental status Seizures Coma ```

Question 35

HHS investigations

Answer 35

The key investigations for management of HHS include a laboratory glucose, urea & electrolytes blood test, a blood gas (venous/arterial) and a blood or urinary ketone level. additional tests looking for potential causes/ complications e.g. ecg

Question 36

management principles of HHS

Answer 36

Aggressive fluid resuscitation: controlled to prevent cerebral oedema 0.9% saline normalise glucose:consider insulin therapy if ketonaemia or slow drop in BM Electrolytes including sodium, potassium, phosphate and magnesium should be monitored regularly (4 hourly minimum) and replaced as necessary. cardiac monitoring LMWH prophylaxis