Endocrinology 2 Flashcards
What is hypothyroidism?
Clinical condition resulting In low levels of free T3/4
Much more common in females (10:1)
What are the causes of hypothyroidism?
Common causes:
Autoimmune: Hashimoto’s thyroiditis - associated with a goitre
Less common:
Drugs - amiodarone, iodine excess, lithium
iodine deficiency: most common cause worldwide
thyroiditis: often transient
Secondary - hypothalamic disorders,pituitary
Rare: Congenital Genesis, neoplastic infiltration
How does Hashimoto’s hypothyroidism come about?
T-cell destruction of the gland, plus B-cell secretion of TPO antibodies
Often initial hyperthyroid phase
symmetrical, bosselated goitre
What are the symptoms of hypothyroidism?
Fatigue Depression/psychosis Cold intolerance Weight gain Constipation menorrhagia myxoedema coma
What are the signs of hypothyroidism?
Hair loss loss of outer 1/3 of eyebrow anaemia hoarse voice goitre bradycardia dry skin hyporeflexia
What investigations are done for hypothyroidism?
FBC: anaemia
Macrocytic if co-morbid pernicious anaemia
Microcytic if menorrhagia
TFTS: raised TSH, reduced free T4 in primary causes
low TSH in pituitary / hypothalamic disease, or ‘sick thyroid syndrome’ due to non-thyroidal illness
TPO antibodies: raised in Hashimoto’s
Cholesterol: can be raised due to hepatic hypothyroidism
CK: raised due to muscle hypothyroidism
What is the management for hypothyroidism?
Levo-thyroxine (L-T4)
low starting dose, titrated up to clinical effect
reassess every 4-6 weeks until TSH is in the lower half of the reference range in primary disease
TSH unreliable if secondary causes, titrate with free T4 levels and clinical symptoms
When does acute thyroiditis occur?
May follow an URTI
What is the presentation of acute thyroiditis?
Fever and malaise, plus thyroid swelling and tenderness - TENDER goitre
Initially there are thyrotoxic features as stored hormone is released. After this, the patient develops hypothyroidism which is usually transient but can occasionally be permanent.
There is classically low / absent uptake on technetium scanning
What is the treatment of acute thyroiditis?
Propanolol in the thyrotoxic phase, and then simple analgesia
Occasionally, prednisolone 30mg is used
What is the most common thyroid carcinoma?
Papillary carcinoma: 70%
What is the common age of papillary carcinoma?
40-50 years old
What are the risk factors for papillary carcinoma?
Previous neck irradiation
How does papillary carcinoma spread?
Locally, and metastasises to local nodes
can go to bone/lung but this is rare
How is papillary carcinoma cured?
By surgical resection, including metastases
Neck lymph node dissection if nodal involvement
Ablative radio-iodine therapy as an adjunct
What is the prognosis for papillary carcinoma?
GOOD
thyroglobulin can be used as a tumour marker following surgery
What % of thyroid carcinomas are follicular carcinomas?
20%
How does follicular thyroid carcinoma metastasise?
Via the bloodstream, classically to bone
How is follicular thyroid carcinoma treated?
Same as papillary carcinoma: surgical resection + lymph node dissection + radio ablative therapy
What % of thyroid cancers are medullary cancers?
5%
Who does medullary cancer tend to affect?
Older adults
Can affect children/young adults as part of multiple endocrine neoplasia syndrome: Men IIa/IIb
Exclude PCC prior to surgery in young patients
Where does Medullary cancer arise from?
Parafollicular ‘C’ cells
Secrete calcitonin, so plasma calcitonin levels are raised
They are slow growing and indolent, metastasising to local nodes, but the prognosis is poor
What % of thyroid cancer cases are anaplastic?
<5% cases
What population does anapaestic cancer arise in?
Elderly populations
How do anaplastic carcinomas spread?
Locally aggressive with rapid and extensive local invasion
Complications of tracheal/SVC
How is anaplastic carcinoma treated?
total thyroidectomy often not possible
External radiotherapy may give palliation
prognosis Is poor
What is the differential for thyroid malignancy?
Lymphoma
What is the presentation of thyroid malignancy?
Most present as asymptomatic thyroid nodules of lymph nodes
May be hoarseness / dysphagia
Thyroid dysfunction = rare
What is the approach to a solitary thyroid nodule?
History/examination
USS
Technetium scans: ‘Hot’ - ?adenoma
‘Cold’ - ?malignancy
FNA and cytology
What does the anterior pituitary synthesise and secrete?
Growth hormone Prolactin Adrenocorticotrophic hormone (ACTH) Thyroid stimulating hormone (TSH) Gonadotrophin luteinising hormone (LH) Follicle stimulating hormone (FSH)
What does the posterior pituitary store and secrete?
ADH
Oxytocin
Where are ADH and oxytocin produced?
In the hypothalamus (connected by the pituitary stalk to the posterior pituitary)
What is a pituitary adenoma?
Benign tumour of the glandular tissue
Can be life threatening due to mass effects or secretory actions
Some are associated with MEN I / IIa syndromes
What is a micro adenoma / macro adenoma?
<1cm = microadenoma
> 1cm = macroadenoma
What is a ‘functioning’ vs ‘non-functioning’ adenoma?
Whether they are secretory or not
What Is the presentation of a non-functioning adenoma?
Bitemporal hemianopia: compression of the optic chiasm
Ocular palsy - compression of cranial nerves III, IV and VI
Hypopituitarism
Signs of raised ICP: headache
hypothalamic compression symptoms: altered appetite, thirst, sleep/wake cycle
What is the presentation of a functioning adenoma?
Acromegaly: excessive GH production
Hyperprolactinaemia: excessive prolactin production
Cushing’s syndrome: excessive ACTH production
These can cause any of the above mass effects
What dies prolactin do?
Stimulates milk production in the breast, and also inhibits GnRH and gonadotrophin production
What are the clinical features of hyperprolactinaemia?
Galactorrhoea: in females, spontaneous / expressible Oligo/amenorrhoea Decreased libido Subfertility in males Arrested puberty in younger patients
In the long term, osteoporosis may develop due to androgen/oestrogen deficiency
What are the other causes of hyperprolactinaemia?
Breast stimulation / stress (transient)
Drug-induced
Idiopathic
How is diagnosis of hyperprolactinaemia done?
Pituitary MRI following raised serum prolactin
How is a prolactinoma treated?
Dopamine agonists: dopamine inhibits prolactin release
Lifelong Ropinarole / Bromocriptine
Shrink tumours down without surgical risk.
Symptoms normally recur on stopping the drugs
What are the side effects / long term effects of dopamine agonists?
S/E: nausea, vomiting, dizziness, syncope
Associated with pulmonary, cardiac and retroperitoneal fibrosis.
Monitor for with CXR and echo.
What does GH do?
What does excess GH cause in children? Adults?
GH: stimulates skeletal ad soft-tissue growth
Excess GH causes gigantism in children (if prior to epiphyseal plate closure).
In adults - acromegaly.
Acromegaly: normally due to pituitary tumour. Rarely, neoplastic disease of GH/GH related proteins from non-pituitary tumours
How is diagnosis of acromegaly done?
Insulin-like Growth Factor 1 (IGF-1) is the initial screening test (raised)
Oral glucose tolerance test whilst measuring growth hormone (high glucose normally suppresses growth hormone)
MRI brain for the pituitary tumour
Refer to ophthalmology for formal visual field testing
What are the symptoms of acromegaly?
Space Occupying Lesion:
Headaches
Visual field defect (“bitemporal hemianopia”)
Overgrowth of tissues
Prominent forehead and brow (“frontal bossing”)
Large nose
Large tongue (“macroglossia”)
Large hands and feet
Large protruding jaw (”prognathism”)
Arthritis from imbalanced growth of joints
GH can cause organ dysfunction
Hypertrophic heart Hypertension Type 2 diabetes Colorectal cancer Symptoms suggesting active raised growth hormone
Development of new skin tags
Profuse sweating
What are the signs of acromegaly?
Protruding mandible Prominent supraorbital ridge Interdental separation Large tongues Spade-line hands/feet Tight rings Visual field defects Hypertension
What is the management of acromegaly?
Somatastatin analogues may be used to shrink the tumour
Short term - prior to surgery
Long term if surgical removal not possible
Pegvisomant (GH antagonist given subcutaneously and daily)
Somatostatin analogues to block GH release (e.g. ocreotide)
Dopamine agonists to block GH release (e.g. bromocriptine
Surgical management: transphenoidal approach; look for scar beneath the upper lip
What is Cushing’s syndrome?
Describes the symptoms of increased circulating glucocorticoid - cortisol
Occurs most commonly from exogenous administration of steroids
Spontaneous forms = rare
What are the ACTH dependent causes of Cushing’s?
Cushing’s DISEASE: Increased ACTH from the pituitary (pituitary adenoma) (65%)
Ectopic ACTH - non-pituitary ACTH secreting tumour (10%). Classically small-cell lung cancer
ACTH independent causes: Excess adrenal cortisol production
Due to an adrenal tumour or nodular hyperplasia: 25%
Subsequent physiological ACTH suppression
What are the symptoms of Cushing’s syndrome?
Round “moon” face Central Obesity Abdominal striae Buffalo Hump (fat pad on upper back) Proximal limb muscle wasting High levels of stress hormone:
Hypertension Cardiac hypertrophy Hyperglycaemia (Type 2 Diabetes) Depression Insomnia Extra effects:
Osteoporosis
Easy bruising and poor skin healing
What are the signs of Cushing’s syndrome?
Moon face Frontal balding Striae Hypertension Pathological fractures 'Buffalo hump' - dorsal fat pad Proximal myopathy
May be hypokalaemia due to the mineralocorticoid activity of cortisol.
A cushingoid appearance can also be caused by excess alcohol consumption
How is the diagnosis of Cushing’s syndrome done?
Confirm raised cortisol
Overnight dexamethasone suppression test:
To perform the test the patient takes a dose of dexamethasone (a synthetic glucocorticoid steroid) at night (i.e. 10pm) and their cortisol and ACTH is measured in the morning (i.e. 9am). The intention is the find out whether the dexamethasone suppresses their normal morning spike of cortisol
How is the dexamethasone suppression test done?
1mg oral dexamethasone given at midnight
Serum cortisol checked before and then at 8am
Normal –> negative feedback leads to cortisol level <50mmol/L
Cushings –> failure to suppress a cortisol secretion
What are the screening tests to confirm Cushing’s syndrome?
48 hour dexamethasone test, 24 hour free cortisol or midnight cortisol.
If any are abnormal, localisation tests are required
If you receive an abnormal low dose dexamethasone test, what is the next step?
HIGH DOSE Dexamethasone suppression test:
2mg/6h PO (total 8mg) for 2d to differentiate between pituitary and ectopic causes
Measure plasma and urinary cortisol at 0 and 48 Hours
Complete/partial suppression –> Cushing’s disease (pituitary) because the pituitary maintains some feedback control
MRI required
NO suppression indicates an ectopic source: do a CXR to find the primary tumour
How does the CRH test work?
CRH is given and cortisol is measured at 2 hours
Raised with pituitary disease but not with ectopic sources
What is the management for pituitary adenoma?
Transphenoidal surgery - apart from prolactinoma
Surgery should not be delayed, as prolonged disc optic chiasmal compression can lead to a permanent loss of vision
What are the other causes of hypothalamic-pituitary disturbance?
Panhypopituitusm
Defective production of all pituitary hormones
What is the presentation of panhypopituitism
What hormone does this suggest a deficiency of?
Fatigue, myalgia, hypotension: GH/corticotrophin deficiency
Diabetes insipidus: ADH deficiency
Hypothyroidism: TSH deficiency
What are the causes of Panhypopituitusm?/
Pituitary causes:
Obliteration of pituitary by primary / metastatic tumour
Surgical removal / irradiation of the pituitary
Ischamic necrosis due to hypotensive shock
Hypothalamic causes: Destruction of the hypothalamus by: primary brain tumour: craniopharyngoma infarction Sarcoid Infection
How is diagnosis of Panhypopituitusm done?
pituitary hormones: low
effector gland hormones: low
Low response to stimulation tests
Imaging to localise the pathology
How do diseases of the neurohypothesis occur?
mainly as a result of damage to the hypothalamus e.g. tumour invasion or infarction
failure of ADH production leads to diabetes insipidus, with polyuria and polydipsia
Excessive ADH production leads to SIADH
What is pheochromocytoma (PCC)?
Catecholamine secreting tumours arising from sympathetic paraganglial cells, known as chromatin cells
Where are PCCs found?
In the adrenal medulla
25% are familial and associated with multiple endocrine neoplasia type 2 (MEN 2).
There is a 10% rule to describe the patterns of tumour:
10% bilateral
10% cancerous
10% outside the adrenal gland
What’s the presentation of PCC?
Severe/episodic Hypertension unresponsive to medical tx
General: sweating, heat intolerance , pallor or flushing
Neurological: Headaches, visual disturbances, seizures
CV: palpitations, chest tightness, dyspnoea, postural hypertension
GI: abdominal pain, nausea, constipation
Symptoms can be worsened by stress, alcohol and drugs
B-blockers can induce life threatening hypertensive episodes in patients without adequate alpha blockade. therefore, labetalol = treatment of choice
How is diagnosis of PCC done?
3 x 24 hour urine collections for free met adrenaline and normetadrenaline
N.B. NICE now suggest metanepherines
MRI/CT/functional imaging to locate the tumour
What is the management of PCC?
Alpha blockers (i.e. phenoxybenzamine)
Beta blockers once established on alpha blockers
Adrenalectomy to remove tumour is the definitive management
What is Addison’s disease?
Primary adrenal insufficiency - autoimmune
Destruction of the ENTIRE adrenal cortex, leading to glucocorticoid (cortisol), mineralocorticoid (aldosterone) and sex-steroid deficiencies
How does Addison’s disease differ from HPA disease?
HPA disease generally spares mineralocorticoid production, which is stimulated by ATII
Sex steroids are also largely independent of pituitary stimulation
Describe the aetiology of Addison’s disease
80% autoimmune in UK
TB = most common worldwide
Sepsis
metastatic cancer: lung/breast
Lymphoma
Adrenal haemorrhage: Waterhouse-Friederichsen syndrome
What are the symptoms of Addison’s disease?
Fatigue Nausea Cramps Abdominal pain Reduced libido Syncope Depression
What are the signs of Addison’s disease?
Pigmentation, especially of new scars and palmar creases
Postural hypotension
Signs of dehydration
Loss of body hair (particularly axillary/pubic)
What investigations should be done for Addison’s disease?
FBC: anaemia
U&Es: low sodium, high potassium, uraemia - due to mineralocorticoid insufficiency
Ca2+: raised
glucose: low due to lack of cortisol
ACTH / synacthen test
9AM ACTH/cortisol
adrenal autoantibodies
CT/MRI
What is the short ACTH stimulation / synacthen test?
Give tetracosactide IM (ACTH analogue)
Measure plasma cortisol before and 30 minutes after
Synthetic ACTH should stimulate cortisol production in adrenals
Second value >550nmol/L excludes Addison’s
Describe how the 9AM ACTH test is done?
Raised ACTH, low/normal cortisol confirms Addison’s
What investigations can be done for the cause of Addison’s
21-hydroxylase adrenal autoantibodies: autoimmune disease
CXR: TB
Adrenal CT: to look for TB / metastatic disease if antibodies negative
What is the management of Addison’s disease?
Long-term glucocorticoid cover
15-25mg hydrocortisone daily, in three divided doses
avoid giving late in day (can cause insomnia)
Long term mineralocorticoid cover: required if postural hypotension, low sodium or high potassium
Fludrocortisone 50-200 micrograms daily
How should steroids be counselled / adjusted?
Steroids should never be abruptly stopped. Extra doses if strenuous exercise
Double dose for surgery, febrile illness or trauma
Carry a steroid card / bracelet and carry IM hydrocortisone in case of Addisonian crisis
What is Addisonian crisis?
Severely inadequate levels of cortisol, occurring either as a first presentation of adrenal disease, or triggered by physiological stress
Presents with fever, nausea, vomiting, shock, hypoglycaemia, hyponatremia and hyperkalaemia
What is the treatment for Addisonian crisis?
IV fluids and IV hydrocortisone
What is CAH?
Congenital deficiency in 21-alpha-hydroxylase
This is necessary for the production of mineralocorticoids and glucocorticoids but NOT sex hormones
What happens to hormone levels in CAH?
Aldosterone and cortisol levels decrease, with consequent ACTH rises
Precursors such as progesterone build up and go down the alternative pathway to form sex hormones
Testosterone levels are raised
What are the clinical features of CAH?
Virilisation of the external genitalia in females: clitoral hypertrophy and variable fusion of the labia
Enlarged penis and pigmented scrotum is seen in teh male, yet this is rarely picked up
Salt-losing crisis in 80% males, at 1-3 weeks of age
in the non salt-losing males, presents as hypervirilisation
Early pubarche, adult body odour, muscular build
What investigations are done for CAH?
17-alpha-hydroxyprogesterone levees: markedly raised
other features may be: low sodium, high potassium and metabolic acidosis in salt losers
What is the management of CAH?
Steroid cover, as per Addison’s disease
Again, at risk of Addisonian crisis
What is Conn’s syndrome?
Adrenal adenoma, leading to primary hyperaldosteronism
Responsible for hyperaldosteronism in 60% cases
Bilateral adrenal hyperplasia is the second most common cause for primary hyperaldosteronsim
LEADS TO SODIUM AND WATER RETENTION
What is the presentation of Conn’s syndrome?
Mostly asymptomatic
HTN - resistant to treatment, may cause headaches
Features of hypokalaemia; may cause cramps, weakness, Tetany. may be polyuria
Biochemical features: hypokalaemia, with urinary potassium loss
Elevated plasma aldosterone:renin ratio
Plasma aldosterone levels will not be suppressed by fludrocortisone administration
What further investigations can be done for Conn’s syndrome?
One primary hyperaldosterone is confirmed, adrenal CT is indicated to differentiate Conn’s from adrenal hyperplasia
can also do adrenal scintigraphy
What is the management of Conn’s syndrome?
Laparoscopic adrenalectomy to remove adenoma
Spironolactone post-op to control hypertension/hypokalaemia (tx of choice for bilateral hyperplasia)
Why is 40% of plasma calcium inactive?
Bound to albumin
How does albumin affect measured calcium
Labs adjust for low/high serum albumin to give e measure of ionised calcium
If low albumin, non-adjusted calcium appears low
How do acidotic/alkalotic states affect ionised calcium levels?
Acidotic states increase ionised calcium by decreasing albumin binding
Alkalotic states decrease ionised calcium by increasing albumin binding
Where are the parathyroid glands?
How many are there?
4
Posterior to thyroid
Which cells secrete PTH?
When is PTH secreted?
Chief cells
Secreted when plasma calcium levels are LOW
PTH can also be secreted in response to low vitamin D or high phosphate levels
How does PTH increase plasma calcium levels?
Directly stimulating calcium reabsorption from bone
Directly increasing renal tubular calcium reabsorption
Indirectly stimulating increased GI calcium absorption: by increasing vitamin D activation in the kidney
PTH has a secondary effector increasing renal phosphate excretion
How does Vitamin D sustain plasma calcium and phosphate levels?
Increasing inflow from GIT
What is Vitamin D used for?
normal bone formation
