Addison’s Disease
Definition & DDx
1º Adrenocortical insufficiency – autoimmune destruction of adrenal cortex leading to
decreased aldosterone and cortisol
2º due to:
- Long term steroid therapy - Meningococcal septicaemia
- TB - Antiphospholipid syndrome
- Metastasis - Pituitary disorders (tumour,
- HIV irradiation, infiltration)
Anatomy & Risks
- In 2º adrenal insufficiency = gradual increase in cortisol with repeated synacthen
o In 2º - both serum cortisol and plasma ACTH low
- In 1º - serum cortisol low but plasma ACTH high
Symptoms & Complications
- Lean, tanned, tired, tearful
o Pigmented palmar creases and buccal mucosa
o Only present in 1º due to ACTH increase stimulating melatonin production
- Vomiting/diarrhoea/constipation/abdo pain
- ‘Salt craving’
Complications
Addisonian Crisis – presents with hypoglycaemia and hypovolaemic shock
Can be triggered by surgery, steroid withdrawal, intercurrent illness, adrenal haemorrhage
- Hydrocortisone 100mg IV stat
- IV fluid bolus for BP support
Investigations
U&Es - If levels <500 then send for Synacthen
- Hyperkalaemia test
- Hyperuraemia
- Hyponatraemia Synacthen Test (Short ACTH Stimulation
- Hypoglycaemia Test)
- Metabolic acidosis - Measure plasma cortisol
- 30mins later administer 250mcg
9am serum cortisol can be performed Synacthen IM
initially in primary care: - Measure plasma cortisol 30mins after
- +ve if cortisol <550mnol/L
Treatment/Management & Side effects
Typical treatment
- Hydrocortisone in 2-3 divided doses daily, e.g., 20mg in morning, 10 in evening
- Consider medical alert bracelet for steroids
- Given hydrocortisone injection for emergencies
During intercurrent illness
- Double glucocorticoids
- Maintain fludrocortisone
,Cushing’s Syndrome
Definition & DDx
Pituitary adenoma causing hypercortisolism – loss of normal feedback mechanism of HPA axis
- Can also be caused by SCLC, adrenal adenoma/hyperplasia, iatrogenic
DDx
- Pseudo-Cushing’s can be caused by alcohol excess
o Use insulin stress test to differentiate
- PCOS
- Adrenal insufficiency
Anatomy & Risks
ACTH-dependent causes ACTH-independent causes
(Adrenocorticotropic hormone which - 1º adrenal diseases
stimulates adrenal gland to produce - Adrenal adenomas/carcinomas
cortisol) - Exogenous steroids
- Excessive ACTH production - Produce cortisol independently of
- Pituitary tumour (Cushing’s disease) ACTH stimulation
- Ectopic ACTH-producing tumours e.g.,
lung carcinoids, thymic carcinoids
Symptoms & Complications
- Central obesity/moon face/buffalo hump/weight gain
- Skin/muscle atrophy/bruises/abdo striae
- Osteoporosis/HTN/diabetes
- Infection/VTE prone
- Mood change/hirsutism/menorrhagia/erectile dysfunction
Investigations
Dexamethasone suppression test (acts on
hypothalamus as -ve feedback) - Measure ACTH
- 1mg Dex given at 10pm o Low = Adrenal Cushing’s
- Level measured 9am o High = Ectopic ACTH
o Low = normal U&Es
o High = Cushing’s syndrome - Hypokalaemia
- If high, 8mg Dex given at 10pm - Hypernatraemia
- Level measured at 9am - Increased bicarb
o Low = Cushing’s Disease o Hypokalaemic alkalosis
o High = ACTH needs measured
Treatment/Management & Side effects
- Selective removal pituitary adenoma
- Bilateral adrenalectomy if source unknown
- Metyrapone (glucocorticoid synthesis inhibitor)
o Leads to increase in ACTH production
, Diabetes Mellitus
Type 1
Definition & DDx
Reduction in insulin action sufficient to cause hyperglycaemic microvascular pathology
Severe insulin deficiency due to autoimmune of pancreatic islets
Symptoms & Complications
Classic triad of symptoms - Increased infections
- Polyuria/nocturia o Including genital itching
- Thirst
- Weight loss
Other common symptoms Complications
- Tiredness - DKA
- Mood changes - Hypoglycaemia
- Blurred vision - HHS
Investigations
Diagnosis
- HbA1c ≥4.8/48 on 2 separate occasions
o Not normally used for Type 1 patients
- Fasting BG ≥7
- 2hr BG OGTT ≥11.1
o Take BM measurement after fasting
o Give 75g glucose
o Measure again after 2 hours
Also, if in doubt:
- Low C-peptide
- Diabetes specific autoantibodies
Treatment/Management & Side effects
Insulin – prescribed by time, brand name, Types
device and dose - Rapid acting (Novorapid)
- Side effects include weight gain, - Short acting (Actrapid)
lipodystrophy, hypos o Normally given IV for DKA
Regimes patients
- Basal bolus - Intermediate (HumulinI)
o Rapid acting TDS - Long acting (Glargine/Lantus,
o Long-acting OD Determir/Levemir, Degludec/Tresiba)
- Intermediate BD e.g., HumulinI (before - Rapid/intermediate mix (Humalogmix)
breakfast, after dinner) - Short/intermediate mix (HumulinM3)
- Mixed e.g., Novomix (before breakfast, Additional:
after dinner) - Add metformin if BMI >25
Do not stop if sick due to DKA risk - Self-testing recommended QDS,
- Maintain normal calorie intake if including before each meal and before
possible and fluids 3-5L/day bed
- Check BMs 1-2hrly - HbA1c measured 3-6mths
Definition & DDx
1º Adrenocortical insufficiency – autoimmune destruction of adrenal cortex leading to
decreased aldosterone and cortisol
2º due to:
- Long term steroid therapy - Meningococcal septicaemia
- TB - Antiphospholipid syndrome
- Metastasis - Pituitary disorders (tumour,
- HIV irradiation, infiltration)
Anatomy & Risks
- In 2º adrenal insufficiency = gradual increase in cortisol with repeated synacthen
o In 2º - both serum cortisol and plasma ACTH low
- In 1º - serum cortisol low but plasma ACTH high
Symptoms & Complications
- Lean, tanned, tired, tearful
o Pigmented palmar creases and buccal mucosa
o Only present in 1º due to ACTH increase stimulating melatonin production
- Vomiting/diarrhoea/constipation/abdo pain
- ‘Salt craving’
Complications
Addisonian Crisis – presents with hypoglycaemia and hypovolaemic shock
Can be triggered by surgery, steroid withdrawal, intercurrent illness, adrenal haemorrhage
- Hydrocortisone 100mg IV stat
- IV fluid bolus for BP support
Investigations
U&Es - If levels <500 then send for Synacthen
- Hyperkalaemia test
- Hyperuraemia
- Hyponatraemia Synacthen Test (Short ACTH Stimulation
- Hypoglycaemia Test)
- Metabolic acidosis - Measure plasma cortisol
- 30mins later administer 250mcg
9am serum cortisol can be performed Synacthen IM
initially in primary care: - Measure plasma cortisol 30mins after
- +ve if cortisol <550mnol/L
Treatment/Management & Side effects
Typical treatment
- Hydrocortisone in 2-3 divided doses daily, e.g., 20mg in morning, 10 in evening
- Consider medical alert bracelet for steroids
- Given hydrocortisone injection for emergencies
During intercurrent illness
- Double glucocorticoids
- Maintain fludrocortisone
,Cushing’s Syndrome
Definition & DDx
Pituitary adenoma causing hypercortisolism – loss of normal feedback mechanism of HPA axis
- Can also be caused by SCLC, adrenal adenoma/hyperplasia, iatrogenic
DDx
- Pseudo-Cushing’s can be caused by alcohol excess
o Use insulin stress test to differentiate
- PCOS
- Adrenal insufficiency
Anatomy & Risks
ACTH-dependent causes ACTH-independent causes
(Adrenocorticotropic hormone which - 1º adrenal diseases
stimulates adrenal gland to produce - Adrenal adenomas/carcinomas
cortisol) - Exogenous steroids
- Excessive ACTH production - Produce cortisol independently of
- Pituitary tumour (Cushing’s disease) ACTH stimulation
- Ectopic ACTH-producing tumours e.g.,
lung carcinoids, thymic carcinoids
Symptoms & Complications
- Central obesity/moon face/buffalo hump/weight gain
- Skin/muscle atrophy/bruises/abdo striae
- Osteoporosis/HTN/diabetes
- Infection/VTE prone
- Mood change/hirsutism/menorrhagia/erectile dysfunction
Investigations
Dexamethasone suppression test (acts on
hypothalamus as -ve feedback) - Measure ACTH
- 1mg Dex given at 10pm o Low = Adrenal Cushing’s
- Level measured 9am o High = Ectopic ACTH
o Low = normal U&Es
o High = Cushing’s syndrome - Hypokalaemia
- If high, 8mg Dex given at 10pm - Hypernatraemia
- Level measured at 9am - Increased bicarb
o Low = Cushing’s Disease o Hypokalaemic alkalosis
o High = ACTH needs measured
Treatment/Management & Side effects
- Selective removal pituitary adenoma
- Bilateral adrenalectomy if source unknown
- Metyrapone (glucocorticoid synthesis inhibitor)
o Leads to increase in ACTH production
, Diabetes Mellitus
Type 1
Definition & DDx
Reduction in insulin action sufficient to cause hyperglycaemic microvascular pathology
Severe insulin deficiency due to autoimmune of pancreatic islets
Symptoms & Complications
Classic triad of symptoms - Increased infections
- Polyuria/nocturia o Including genital itching
- Thirst
- Weight loss
Other common symptoms Complications
- Tiredness - DKA
- Mood changes - Hypoglycaemia
- Blurred vision - HHS
Investigations
Diagnosis
- HbA1c ≥4.8/48 on 2 separate occasions
o Not normally used for Type 1 patients
- Fasting BG ≥7
- 2hr BG OGTT ≥11.1
o Take BM measurement after fasting
o Give 75g glucose
o Measure again after 2 hours
Also, if in doubt:
- Low C-peptide
- Diabetes specific autoantibodies
Treatment/Management & Side effects
Insulin – prescribed by time, brand name, Types
device and dose - Rapid acting (Novorapid)
- Side effects include weight gain, - Short acting (Actrapid)
lipodystrophy, hypos o Normally given IV for DKA
Regimes patients
- Basal bolus - Intermediate (HumulinI)
o Rapid acting TDS - Long acting (Glargine/Lantus,
o Long-acting OD Determir/Levemir, Degludec/Tresiba)
- Intermediate BD e.g., HumulinI (before - Rapid/intermediate mix (Humalogmix)
breakfast, after dinner) - Short/intermediate mix (HumulinM3)
- Mixed e.g., Novomix (before breakfast, Additional:
after dinner) - Add metformin if BMI >25
Do not stop if sick due to DKA risk - Self-testing recommended QDS,
- Maintain normal calorie intake if including before each meal and before
possible and fluids 3-5L/day bed
- Check BMs 1-2hrly - HbA1c measured 3-6mths
