Acromegaly, Hypopituitarism & Cushing's Flashcards
Cause of acromegaly.
Almost exclusively GH-secreting pituitary tumour.
Risks of untreated acromegaly.
Disfiguring features
Premature death from CVS disease.
Increased risk of bowel cancer
Clinical features of acromegaly.
Increased size of hands and feet.
Coarse facial features with frontal bossing of forehead and protrusion of chin and widely spaced teeth.
Enlargement of tongue and soft-palate which leads to snoring and sleep apnoea.
Puffiness of hands with carpal tunnel syndrome.
Amenorrhoea
Decreased libido
Headaches
Sweating
Snoring
“My rings don’t fit, nor my old shoes, and now I’ve got a wonky bite and curly hair. I put on lots of weight, all muscle and looked good for a while. Now I look so haggard”.
Specific features of acromegaly due to GH secretion.
Sweating
Headache
Hypertension
Diabetes Mellitus
Investigations done for acromegaly.
Oral glucose tolerance test (OGTT)
IGF-1 assay.
Glucose, Ca2+ and PO43- all increased.
Don’t rely on random GH since is is pulsatile and can increase with other factors as well.
MRI scan of pituitary fossa
Visual fields and acuity
ECG and ECHO.
Ask patient to show old photos.
Explain OGTT and IGF-1 testing in acromegaly.
Failure to suppress GH after OGTT as well as elevated IGF-1 levels are found in active acromegaly.
Some acromegaly tumours also secrete another hormone along GH.
Which?
Prolactin
This is because they share the same cell origin.
What imaging can be done in acromegaly tumour?
MRI will usually show.
Micro-adenomas may only be visible with contrast enhanced scans.
Types of treatment of acromegaly.
Surgery
Medical treatment
External beam radiotherapy
Stereotactic radiotherapy (gamma knife)
What is the treatment of choice for most patients?
Surgery
Surgical remission in acromegaly adenomas.
High likelihood of surgical remission in microadenomas
Remission only achieved in approx. 60% of patients with macro-adenomas.
What is given as medical treatment for acromegaly?
Somatostatin analogues
How is somatostain analogues administered?
Monthly subcut injection
What otherm medications can be given to treat acromegaly?
GH receptor blockers may control IGF-1 levels in refractory acromegaly.
Dopamine agonists may control GH in certain patients as well.
When is stereotactic radiotherapy suitable?
When the lesion is well away from the optic chiasm.
Issues with radiotherapy in acromegaly.
May take many years to lower GH.
There are also long-term side effects such as gradual onset hypopituitarism and possible cerebrovascular disease.
After initial surgery of acromegaly tumour what is done?
A repeat OGTT to indicate whether there is persisent disease even after surgery.
What other long-term follow ups after surgery of acromegaly is done?
Ensure adequate control of GH and IGF-1 levels and exclude recurrence.
Periodic screening of colonoscopy due to the risk of neoplasia.
Sleep apnoea, diabetes and CVS risk assessment.
Usual presentation of non-functioning pituitary adenomas (NFPAs).
Visual field loss
Headache
Hypopituitarism
How is this diagnosis increasingly made?
As a pituitary incidentaloma meaning that it is discovered for unrelated reasons.
When is surgery made for NFPAs?
If there is a visual field defect or threat to vision.
Usual route for NFPA surgery.
Trans-sphenoidal
Sometimes trans-cranial if need be.
Histological markers that may present in NFPAs
Positive immunostaining for biologically inactive FSH and LH.
They do not secrete bio-active hormones however.
Most common cause of acquired hypopituitarism.
Pituitary tumour
Less common causes of acquried hypopituitarism.
Inflammatory and infiltrative disorders which are usually associated with Diabetes Insipidus as well.
Traumatic brain injury
Radiotherapy
1 - Hypothalmus => Kallman’s syndrome, tumour, inflammation, infection, ischaemia.
2 - Pituitary stalk => Trauma, surgery, mass lesion (Craniopharyngioma), meningioma, carotid artery aneurysm.
3 - Pituitary => Tumour, irradiation, inflammation, autoimmunity, infiltration, ischaemia.
In what order are hormones affected in hypopituitarism?
GH
Gonadotropins
TSH
ACTH
PRL
Clinical features of hypopituitarism.
Often non-specific symptoms such as lethargy, weight gain and sexual dysfunction.
Medical emergency of hypopituitarism.
Hypo-adrenal crisis with hyponatraemia and hypotension.
What might be a specific feature for hypopituitarism in children?
Short stature
What is the assessment of exclusion when investigating hypopituitarism?
Adrenal insufficiency
Secondary hypothyroidism investigation.
Low t4 and non-elevated TSH.
Secondary hypogonadism investigation.
Low levels of sex hormones and non-elevated FSH and LH.
What is a good screening test for hypopituitarism in post-menopausal females?
LH and FSH levels since gonadtrophins should be elevated at this age.
GH deficiency investigation.
Low or low-normal IGF-1 levels.
MRI findings in hypopituitarism.
Might show an empty fossa or pituitary tumour.
Treatment of ACTH def.
Hydrocortisone replacement
Treatment of TSH def.
Thyroxine replacement
Doses titrated according to symptomatic imporvement and fT4 levels.
Treatment of gonadotropin def. in men.
With testosterone replacement both for symptom control and protection against osteoporosis.
How is testosterone replacement administered?
By gel or injection.
Treatment of gonadotropin def. in women.
Oestrogen and progesterone replacement.
How are oestrogen and progesterone administered?
COCP or HRT
Treatment of GH def.
GH given daily as a subcut injection.
Treatment of hypopituitarism.
Refer to endocrinology for assessment of pituitary function.
Hydrocortisone if 2ndary adrenal failure
Thyroxine if hypothyroid
HRT or testosterone gel if hypogonadism.
Gonadotropin therapy is needed to induce fertility in both sexes.
Somatotrophin, GH etc….
Clinical features of Cushing’s.
Central obesity
Dorso-cervical fat pads (buffalo hump)
Increased roundness of face.
Plethoric (red) face
Thin skin
Easy bruising
Proximal myopathy
Other signs of Cushing’s
Hypertension
Premature osteoporosis
Diabetes Mellitus
What can happen if Cushing’s is left untreated?
Associated with significant morbidity (5 year mortality of 50%)
What is pseudocushings?
It looks like Cushing’s meaning patients might look Cushingoid or have blood abnormalities similar to Cushing’s.
However it is not Cushings.
Give causes of pseudocushings.
Alcoholism
Severe depression
How can you distinguish between Pseudocushings and Cushings?
Usually in pseudocushings the screening tests will be normal.
Give examples of screening tests for Cushings.
24h Urine Free Cortisol (UFC)
Low Dose Dexamethasone Suppression Test (LDDST)
Overnight Dexamethasone Suppression Test (DST)
What result of 24h UFC suggests Cushings?
Elevated Urine Free Cortisol
What result of LDDST suggests Cushings?
Failure to suppress cortisol to <50 nmol/L
What result of DST suggests Cushings?
Failure to suppress cortisol to <50 nmol/L.
What is a new convenient outpatient screening test of Cushings?
Elevated late night salivary cortisol levels.
4 potential broad causes of Cushings.
Pituitary
Adrenal
Ectopic ACTH
Medication
What is more common, pituitary or ectopic ACTH?
Pituitary
What is usually suggestive of ectopic ACTH tumour?
Hypokalaemia
History of smoking
Weight loss
Due to lung cancer or another malignancy like bronchial carcinoid.
What does a significant and accelerated hirsuitism in Cushing’s suggest?
Adrenal tumour
If ACTH is low what is the most likely cause of Cushing’s?
Adrenal tumour or over-medication
If ACTH is normal or high in Cushing’s, what is the likely diagnosis?
Pituitary or ectopic.
How can you distinguish between ectopic or pituitary Cushing’s?
CRH test
High dose DST
Explain CRH test differences in ectopic and pituitary Cushings.
In pituitary CRH will cause an exaggerated rise in ACTH and cortisol.
In ectopic CRH will be met with a flat response.
Explain High dose DST differences in ectopic vs pituitary Cushings.
The DST will suppress ACTH to some degree in pituitary but not at all in ectopic.
If tests suggests pituitary Cushings, which imaging should be performed?
MRI
If there is no clear pituitary lesion on MRI, what could help confirm diagnosis?
Inferior Petrosal Sinus Sampling
How might IPSS help?
It can confirm central ACTH secretion by showing a clear gradient between central and peripheral ACTH levels after CRH injection.
The inferior petrosal sinus is where the pituitary gland drains. This means that it gives a central ACTH measure.
If central ACTH levels increase in response to CRH compared to peripheral it suggests a pituitary cause.
If ectopic Cushing’s is suspected, what imaging is done?
Whole body CT as well as PET scan which may reveal carcinoma elsewhere (commonly in thorax region)
Management of adrenal Cushing’s.
Laparoscopic adrenalectomy.
Management of Ectopic Cushing’s.
Appropriate treatment of the underlying malignancy and medical control of cortisol levels.
Management of Cushing’s disease.
Transphenoidal removal of the pituitary adenoma.
Give examples of medical treatment of Cushing’s syndrome.
Metyrapone
Ketoconazole
Possibly radiotherapy.
Explain how to perform overnight dexamethasone suppression test.
A good outpatient test.
Dexamethasone 1mg PO at midnight.
Do serum cortisol at 8am
Normally, cortisol suppresses to <50nmol/L but if there is no suppression in cortisol then suspect a Cushing’s cause.
If 1st line tests are abnormal (Overnight DST or 24h urinary free cortisol)
Then do 2nd line tests like 48h DST or 48h High-dose DST.
Explain how to do them.
Give dexamethasone for 2 days.
Measure cortisol at 0 ad 48h.
There should be a failure to suppress levels of cortisol.
48h HD may distinguish pituitary cause from others.
Why might cortisol levels come back abnormal on a random cortisol test?
Because cortisol might be elevated due to something else.
Ilness, time of day and stress can influence results.
Stress such as venepuncture can be enough to increase cortisol
