Elderly - British Geriatrics Society · ACTH deficiency Hypovolaemic Hypoadrenalism Primary salt...
Transcript of Elderly - British Geriatrics Society · ACTH deficiency Hypovolaemic Hypoadrenalism Primary salt...
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Endocrine Disease in the
Elderly
Miles Levy
Consultant Endocrinologist
Leicester Royal Infirmary
BGS Trent Region Autumn Meeting
3rd October 2018
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Overview of talk
• Common endocrine incidental findings
• Particular reference to elderly patients
• Things you might come across in real life
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Topics covered
• Thyroid
• Sodium
• Pituitary
• Adrenal
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Thyroid case
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Case 1
• 79 year-old female
• Fall at home
• Weaker than usual
• Paroxysmal AF
• Permanent Pacemaker
• Osteoporosis
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Case 1
• Alendronic acid 70mg / week
• Apixaban 5mg
• Amlodipine 10mg
• Furosemide 40mg
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Examination
• Pulse 80/min
• Sinus rhythm
• Not dehydrated
• Proximal muscle weakness
• No other findings
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Case 1
• Na 144 mmol/l
• K 3.8 mmol/l
• U 5.2 mmol/l
• C 65 umol/l
• eGFR 81 ml/min
• FBC normal
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Chest X-Ray
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CT thorax
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Thyroid function tests
• T4 20 pmol/L (9-25)
• TSH < 0.05 (0.35-5)
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Questions
• Should we worry about these TFTs?
• What further investigations are needed?
• Does the patient need to be treated?
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Spectrum of disease
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Causes of a low TSH
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High T4/T3
Low TSH
Graves’
Multinodular goitre
Toxic nodule
Thyroiditis
Amiodarone
Excess thyroxineLow T4/T3
Low / normal
TSH
High T4/T3
Normal / high
TSHLow T4/T3
High TSH
Normal T4/T3
Low TSH
Normal T4/T3
High TSH
High T4/T3
Low TSH
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Low T4/T3
Low / normal
TSH
Central hypothyroidism
Isolated TSH deficiency
Non Thyroid IllnessHigh T4/T3
Low TSH
Low T4/T3
Low / normal
TSH
High T4/T3
Normal / high
TSHLow T4/T3
High TSH
Normal T4/T3
Low TSH
Normal T4/T3
High TSH
High T4/T3
Low TSH
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Low T4/T3
High TSH
Normal T4/T3
Low TSH
Normal T4/T3
High TSH
High T4/T3
Low TSH
Sub-clinical hyperthyroidism
Recent treatment hyperthyroidism
Low T4/T3
Low / normal
TSH
High T4/T3
Normal / high
TSHLow T4/T3
High TSH
Normal T4/T3
Low TSH
Normal T4/T3
High TSH
High T4/T3
Low TSH
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Our patient
• T4 20 pmol/L (9-25)
• TSH < 0.05 (0.35-5)
• Unlikely to be sick euthyroid
• LH 80 iU/L, FSH 76 iu/L
• T3 6.4 (3.5-6.5)
• Multinodular goitre
not hypopituitarism
upper normal
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Sub-clinical hyperthyroidism
• Normal T4/T3 with suppressed TSH
• Causes are the same as overt
hyperthyroidismGraves’
Multinodular goitre
Toxic nodule
Thyroiditis
Amiodarone
Excess thyroxine
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Sub-clinical hyperthyroidism
• T3 often at high end of reference range
• Commonly due to autonomous thyroid
nodule in the elderly
• Consider auto-immune
• TPO / TSHr Ab
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Potential consequences
• Progression to overt hyperthyroidism
• Cardiovascular conditions
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Increased risk of AF
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Increased Cardiovascular Mortality
Ten year cardiovascular mortality (Kaplan-
Meier) based on TSH
60
70
80
90
100
0 1 2 3 4 5 6 7 8 9 10
Year
Su
rviv
al
CV
D %
<0.5
0.5-1.2
1.3-2.0
2.1-5
>5
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Other potential consequences
• Increased risk of osteoporotic fractures1
• Increased risk of frailty > 652
• Possible association with dementia3
1 Blum et al., JAMA 2015; 2 Virgini et al. J Clin Endo 2015; 3 Aubert et al Clin Endo 2017
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Considerations the elderly
• Older patients are often asymptomatic
• Apathetic thyrotoxicosis
• Proximal myopathy
• Nodular thyroid disease
• Increased CVS risk
• Osteoporosis
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Whether to treat
• No randomised trials
• Uncontrolled studies have shown CVS
benefit
• In the end it is a clinical judgement call
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Our patient
• Repeat TFTs 12 weeks same results
• Trial of carbimazole 10mg
• Improvement in symptoms
• Normalisation of TSH
• Consideration for radio-active iodine
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Management of thyrotoxicosis
• Carbimazole or PTU
• Radio-iodine
• Surgery
agranulocytosis
hypothyroidism / RAI protection
laryngeal nerve palsy and hypocalcaemia
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Thyroid nodules in elderly
• Very common incidental finding
• Best investigation is ultrasound
• Clinical clues for malignancy and LN
• Anaplastic carcinoma is very rare
• Retrosternal goitres can usually be left
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Sodium case
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Case 2
• Acute Medical Unit
• 80 year old lady
• Weight loss
• Dizziness
• Unwell
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Case 2
• Underweight but not cachectic
• Euvolaemic clinically
• No other findings
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Case 2
• Na 127 mmol/L
• K 3.8 mmol/L
• U 3.6 mmol/L
• C 49 μmol/L
• CRP < 5
• FBC normalnormal CXR
mild hyponatraemia
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Summary
• 80 year old lady with mild hyponatraemia
• What is the diagnostic approach?
• What are the implications in older people?
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Acute severe hyponatraemia v
chronic
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Diagnostic pathway
hyponatraemia
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Urine osmolality
Taking
diuretics or
ACEi
< 100 > 100
Primary
polydipsia
Urine Na
< 30 mmol/L
Urine Na
> 30 mmol/L
Hypervolaemic
CCF
Nephrotic
Cirrhosis
Hypovolaemic
GI loss
3rd Space loss
Euvolaemic
SIADH
ACTH deficiency
Hypovolaemic
Hypoadrenalism
Primary salt
wasting
Consider all
causes
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Our patient
• Serum osmo 256
• Urine osmo 498
• Urine Na 126
low
> 100
> 30
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Urine osmolality
Taking
diuretics or
ACEi
< 100 > 100
Primary
polydipsia
Urine Na
< 30 mmol/L
Urine Na
> 30 mmol/L
Hypervolaemic
CCF
Nephrotic
Cirrhosis
Hypovolaemic
GI loss
3rd Space loss
Euvolaemic
SIADH
ACTH deficiency
Hypovolaemic
Hypoadrenalism
Primary salt
wasting
Consider all
causes
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Further investigations
• Cortisol 267 500 nmol/L
• T4 9 pmol/L (9-25)
• TSH 3.7 miU/L (3.5-5)
• LH 1 miU/L
• FSH 2.4 miU/L
• Prolactin 1407 iU/L
• Suggestive of pituitary disease
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MRI pituitary fossa
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Diagnosis• Pituitary macro-adenoma
• Hyponatraemia due to ACTH deficiency
• Dramatic improvement on hydrocortisone
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Points for discussion
• Hyponatraemia and cortisol deficiency
• Incidental pituitary mass
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Vasopressin and cortisol
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Hyponatraemia and ACTH deficiency
• Looks identical to SIADH
• Different to mechanism of hyponatraemaia
in Addison’s disease (mineralocorticoid)
Hyperkalaemia and pigmentation
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Clinical relevance in elderly
• Do not assume diagnosis of SIADH
• Treatment with hydrocortisone life-
changing
• Consider ACTH suppression in all
hyponatraemic patients on prednisolone
• Increase steroid dose during inter-current
illness or consider parenteral
adminstration
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Hyponatraemia in the elderly
• 30% of all in-patients
• Increased recognition of morbidity
• Associated with increased risk of falls
• Increased osteoporosis and fractures
• Impaired cognition and co-ordination
Corona et al. Clin Endo 2018
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Incidental pituitary mass
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Pituitary incidentaloma
Small low density lesion in pituitary gland
< 1cm diameterBGS Trent A
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Pituitary Micro-adenoma
• Very common
• Up to 1 in 10 MRI scans
• No need for dynamic endocrine
assessment
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Approach to pituitary micro-adenoma
• Consider clinical evidence of hyper-
secretion
• Basal pituitary blood tests
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Acromegaly
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Cushing’s disease
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Biochemical test for acromegaly
• Oral Glucose Tolerance Test
• GH suppresses < 1μg/L in normals
• Elevated serum IGF-1 level
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Biochemical test for Cushing’s
• 24h urine free cortisol
• Overnight dexamethasone suppression
test
• Low dose dexamethasone suppression
test
• Cortisol < 50nmol/L
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Basal pituitary function tests
• LH / FSH / testo in men
• LH / FSH / E2 in women
• Prolactin
• fT4 / TSH
• GH / IGF-1
• 0900 cortisol
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Pituitary Macro-adenoma
> 1cm diameterBGS Trent A
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Pituitary Macro-adenoma• Less common than micro-adenomas
• 1 in 500 MRI scans
• Visual field assessment
• Consider acromegaly and Cushing’s
• Basal pituitary blood tests
• Dynamic assessment of reserve
• Follow up imaging in 12 months
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Temporal visual field loss
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Dynamic pituitary assessment
• Cortisol status
• GH reserve
• Easily done in endocrine unit
• GH replacement may improve quality of
life
synacthen test
glucagon stimulation test
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In-patients with hypopituitarism• Often on full replacement
• Hydrocortisone
• Thyroxine
• Growth hormone
• Desmopressin
may need IM or IV
vital not to omit
no need to change dose
OK to omit
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Desmopressin during intercurrent
illness• Synthetic vasopressin (DDAVP)
• Treatment of Cranial Diabetes Insipidus
• Severe dehydration and hypernatraemia
• Preventable deaths reported
make sure patients with DI
get desmopressin
and fluids
BGS Trent A
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Hypernatraemia in the elderly
• Strong association with frailty
• Suggests profound water deficit
• Poor prognostic sign
• Fluid balance is key
• Always consider DIUrine volume > 3L / 24 h
Urine osmolality < 600
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Adrenal cases
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Case 3
48 year old lady
CTPA for suspected PE
No previous history
PE excluded
1.5cm left adrenal lesion
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Questions
Is this a concern?
Are any tests needed?
Is a follow up scan required?
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Adrenal incidentaloma
Very common (3-10%)
Sensible guidelines1
< 4cm in diameter
Radiologically benign
Non-functional
1 Fassnacht et al. ESE 2016
Can discharge patient
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Quick revision of adrenal gland
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Normal adrenal histology
Adrenal
Cortex
Adrenal
Medulla
ZG
ZF
ZR
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Biochemical tests
ZG
ZF
ZR
Primary hyperaldosteronism
Hypertension and hypokalaemia
Cushing’s syndrome
Autonomous cortisol secretion
Virilisation in a female
Gynaecomastia in a male
Medulla
Cortex
Catecholamine excess
Suspicion of phaeochromocytoma
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Biochemical tests
ZG
ZF
ZR
Blood pressure, serum potassium
Aldosterone / renin ratio
24h UFC
Dexamethasone Suppression Test
Testosterone
17-Hydroxyprogesterone
Medulla
Cortex
24h urine catecholamines
Metanephrines
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Radiology for adrenals
Non-contrast CT adrenals
Fatty lumps benign and homogenous
Low intensity on CT
If indeterminate then options are• Different scan straight away
• Repeat imaging in 6-12 months
No real role for adrenal biopsy unless cancer elsewhere
Hounsfield Units < 10
contrast-enhanced washout CT or MRI
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Non-benign looking lesions
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Screening for cortisol secretion
Overt Cushing’s syndrome
Not Cushingoid in appearance
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Biochemical screening for Cushing’s
1mg overnight dexamethasone suppression test
Cortisol < 50 nmol/L is normal
Cortisol 51-138nmol/L is possibly not
‘Possible autonomous cortisol secretion’
BGS Trent A
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Possible autonomous cortisol secretion
Previously called ‘sub-clinical Cushing’s
Seems to be associated with cardiovascular risk
A relative indication for surgery
Probably warrant follow up
Watch this space…..
BGS Trent A
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Case 4
73 year old lady
Abdominal discomfort and bloating
Bowel cancer screening FOB +ve
Colonoscopy showed R colonic tumour
CT scan 3.6cm right adrenal mass
Due for surgery next week
biopsy malignant
BGS Trent A
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CT scan
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FDG-PET
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Questions
What is the single most important test before operation?
Should the adrenal gland be removed at the same time?
BGS Trent A
utumn 2
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Questions
Indication for rapid turnaround for plasma metanephrines
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Questions
What is the single most important test before operation?
Should the adrenal gland be removed at the same time?
Deal with it later
Bowel cancer priorityBGS Trent A
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Case 5
67 year old male
Hypotension and hypokalaemia
K+ 2.7 mmol/l
Aldosterone 902 pmol/L
Renin 4 mU/L
CT bilateral adrenal nodules
BGS Trent A
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Metomidate PET scan
BGS Trent A
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Case 5
Right Conn’s adenoma
Functional imaging helpful
Referred for surgery
BGS Trent A
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Case 6
78 year old man
Weight loss and muscle weakness
3.7cm right adrenal mass
Calcification and cystic centre
BGS Trent A
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Case 6
24h urine
Plasma
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Case 6
Phaeochromocytoma
Alpha-Blockade
Beta-Blockade
Adrenalectomy
BGS Trent A
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Case 7
75 year old lady
Hypertension
Type 2 Diabetes
Ischaemic Heart Disease
3cm left adrenal massNot Cushingoid
BGS Trent A
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Case 7
Plasma metanephrines normal
24h UFC normal
Post-dex cortisol 322 nmo/L
ACTH 6 (low-ish)
autonomous cortisol secretion
BGS Trent A
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Case 7
Slight increase in size of adrenal mass
Diabetes and hypertension worse
Laparoscopic adrenalectomy
Significant improvement diabetes, BP, weight
Reduction in cardiovascular risk
Probably Cushing’s syndrome
BGS Trent A
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Adrenal incidentaloma summary
Very common (3-10%)
Sensible guidelines1
< 4cm in diameter
Radiologically benign
Non-functional
1 Fassnacht et al. ESE 2016
Can discharge patient
BGS Trent A
utumn 2
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Topics covered
• Thyroid
• Sodium
• Pituitary
• Adrenal
Sub-clinical hyperthyroidism and nodules
Approach to investigation
Investigation of incidental mass
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Overview of talk
• Common endocrine incidental findings
• Particular reference to elderly patients
• Things you might come across in real life
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The End
BGS Trent A
utumn 2
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