Endocrinology Flashcards
Define Graves’ Disease
An autoimmune hyperthyroid condition associated with orbitopathy, pretibial myxoedema and acropachy. It is caused by TSH receptor antibodies. It is the most common form of hyperthyroidism.
Explain the aetiology of Graves’ Disease
Graves’ is an autoimmune disease
The immune system produces an antibody which mimics TSH
TSH receptor antibodies are produced and stimulate the thyroid gland
This leads to thyroid hormone overproduction and enlargement of the thyroid gland to produce a goitre which can be seen on a scintigram
Graves’ is caused by a combination of genetic and environmental factors.
What are the risk factors of Graves’ Disease?
Family history of autoimmune thyroid disease Female sex Smoking High iodine intake Long-term lithium therapy Radiation Radioiodine treatment for benign nodular goitre Trauma to the thyroid gland Toxic multinodular goitre HAART
Moderate alcohol consumption reduces the risk
Summarise the epidemiology of Graves’ Disease
Graves’ is the most common form of hyperthyroidism
More common in women
Prevalence is lower in Black patients
Rarely occurs in children
25% of Graves’ patients have orbitopathy
What are the presenting symptoms of Graves’ Disease?
Heat intolerance - higher body temperature (feel hot when those around are cold) Sweating Weight loss with increased appetite Palpitations (AF or other SVTs) Tremor Irritability Hair loss - outer third of eyebrow, scalp Weakness Diarrhoea Anxiety Loss of libido Oligomenorrhoea/amenorrhoea
What are the signs on physical examination of Graves’ disease?
Tachycardia Diffuse smoothly enlarged goitre Orbitopathy - upper eyelid retraction, exophthalmos, extraocular muscle involvement Cardiac flow murmur Thyroid bruit Pretibial myxoedema Acropachy Palmar erythema Sweaty and warm palms Fine tremor Hair thinning Brisk reflexes Proximal myopathy Lid lag Gynaecomastia
What are the appropriate investigations for Graves’ Disease?
TSH - suppressed
Serum free or total T3 or T4 - elevated (test for T4 first)
Calculate total T3/T4 - high compared with thyroiditis
Radioactive iodine or technetium-99 uptake - elevated
Thyroid isotope uptake scan - diffuse enlargement
TSH receptor antibodies - positive
Anti-thyroid peroxidase antibody
Anti-thyroglobulin antibodies
Thyroid USS - enlarged, highly vascular
CT or MRI orbit - may show muscle thickening
Define phaeochromocytoma
A usually benign tumour of the chromaffin cells in the adrenal medulla leading to excess release of catecholamines.
80-90% of the tumours are adrenal
10% are extra-adrenal (usually head or neck)
10% are bilateral and 10% are malignant
Summarise the aetiology of phaechromocytoma
Mostly sporadic
Approximately 40% are due to genetic conditions
Multiple Endocrine Neoplasia type 2A and 2B - mutation in RET protooncogene
Von Hippel-Lindau disease - mutation in VHL tumour suppressor gene
Neurofibromatosis type 1 - mutation in NF1 for neurofibromin tumour suppressor
Genetic causes mean patients present earlier with bilateral disease and extra-adrenal tumours
Summarise the epidemiology of phaeochromocytoma
Very rare cause of secondary hypertension
Equal in men and women
Seen in all races
Average age at diagnosis = 42y/o
What are the presenting symptoms of phaeochromocytoma?
Episodic/PAROXYSMAL
Palpitations Headaches Sweating Tremor Anxiety Chest pain Dyspnoea Epigastric pain Nausea Constipation Weakness
What are the signs on physical examination of phaeochromocytoma?
Paroxysmal hypertension Tachycardia Pallor Hypertensive retinopathy Orthostatic hypotension Papilloedema Fever Weight loss
What are the appropriate investigations for phaeochromocytoma?
Serum and urine catecholamines - elevated
Urine metanephrine (breakdown product) - elevated
USS/CT to identify location of phaeochromocytoma
I-MIBG scintigraphy (another way of visualising the tumour)
Screen for associated conditions
Genetic testing
Define carcinoid syndrome
Carcinoid syndrome is when symptoms such as diarrhoea, itching, shortness of breath and flushing are caused be a tumour of neuroendocrine cells (a carcinoid tumour) releasing excess histamine, serotonin, bradykinin and prostaglandins.
Explain the aetiology of carcinoid syndrome
Carcinoid tumours are slow growing neuroendocrine tumours
They are mostly derived from serotonin producing enterochromaffin cells
They produce hormones: Serotonin Histamine Bradykinin Prostaglandin
75-80% of patients with carcinoid syndrome have small bowel carcinoids
Symptoms do not occur until there are liver metastases as the hormones are usually metabolised by the liver.
Primary tumour usually in: Small/large intestine Ovaries Stomach Pancreas Thymus Lungs Liver
Summarise the epidemiology of carcinoid syndrome
Slightly more common in males
Most common in 60s-70s
Greater incidence in black patients
Lower incidence in Asian and Hispanics
Carcinoid tumours are the most common functional neuroendocrine tumour.
RARE: UK incidence: 1/1,000,000
Asymptomatic carcinoid tumours are more common
10% of patients with MEN-1 have carcinoid tumours
Multiple endocrine neoplasia type 1 is a hereditary condition associated with tumours of endocrine glands
What are the presenting symptoms of carcinoid syndrome?
Vasoconstriction, increased motility and peristalsis in GI tract and fibroblasts in heart stimulated by serotonin
Diarrhoea Wheeze Shortness of breath Flushing Itching Abdominal pain Palpitations
Symptoms are made worse by alcohol or stress
What are the signs on physical examination of carcinoid syndrome?
Telangiectasia
Flushing
Signs of right heart failure - raised JVP, peripheral oedema
Cardiac murmurs - fibrosis of right sided heart valves
Hepatomegaly if liver mets
Wheeze
Carcinoid Crisis Signs: Profound flushing, Bronchospasm, Tachycardia, Fluctuating blood pressure
What are the appropriate investigations for carcinoid syndrome?
24 hours urine collection: Check 5 HIAA levels (metabolite of serotonin) – elevated
Plasma chromogranin A and B (fasting gut hormones) - elevated if liver mets
Creatinine (elevated) due to dehydration
CT or MRI Scan: To localise the tumour
Radioisotope Scan - OCTREOSCAN: Radiolabelled somatostatin analogue helps localise the tumour
Investigations for MEN-1
Define hyperparathyroidism
A condition in which parathyroid hormone is in excess, resulting in deranged calcium metabolism.
Primary hyperparathyroidism is when PTH is high with a high calcium and low phosphate. PTH secretion is autonomous and unrelated to blood calcium.
Secondary hyperparathyroidism is when PTH is high secondary to a hypocalcaemia and phosphate is high.
Tertiary hyperparathyroidism is when PTH is high, calcium is high and phosphate depends on if the patient has had a kidney transplant.
Summarise the aetiology of hyperparathyroidism
Primary:
Adenoma of the parathyroid gland
Multiple Endocrine Neoplasia
Hyperplasia
Secondary:
Chronic kidney disease
Low vitamin D due to lack of dietary intake, lack of sun exposure or malabsorption
Tertiary:
Occurs after long-term secondary hyperparathyroidism
Summarise the epidemiology of hyperparathyroidism
Primary hyperparathyroidism has an incidence of 5 in 100,000 people
Twice as common in females
Peak incidence of 40-60 years
What are the presenting symptoms of hyperparathyroidism?
Primary: Symptoms of hypercalcaemia Bone pain Generalised abdominal pain Nausea Vomiting Constipation Indigestion Polyuria Depression Confusion Memory loss Fatigue Muscle weakness
Secondary: Symptoms of hypocalcaemia Muscle cramps, tetany and tingling Paraesthesia (hands, mouth, feet and lips) Convulsions
What are the signs on physical examination of hyperparathyroidism?
Primary:
Weak or absent reflexes
Muscle weakness
Secondary:
Positive Chvostek’s sign - tapping skin overlapping facial nerve causes facial muscle contraction
Trousseau sign
What are the appropriate investigations for hyperparathyroidism?
Serum calcium - high in primary/tertiary, low in secondary
Serum PTH - elevated
Serum 25-hydroxy-vitamin D - low in secondary hyperparathyroidism
Urinary PTH - high
Urinarlysis - hypercalciuria if primary
ECG - may see bradycardia, heart block, Osborn wave due to primary
Serum albumin to ensure not pseudohyperparathyroidism
What is the management of hyperparathyroidism?
Primary:
Surgical parathyroidectomy
Calcimimetics eg oral cinacalcet
Bisphopshonates if patient has osteoporosis
Acute Hypercalcaemia: IV Fluids Avoid factors that exacerbate hypercalcaemia (e.g. thiazide diuretics) Maintain adequate hydration Moderate calcium and vitamin D intake
Secondary hyperparathyroidism:
Treat the underlying cause
Give calcium/vitamin D if needed
What are the possible complications of hyperparathyroidism?
Primary:
Increased bone resorption, tubular Ca resorption and 1-alpha-hydroxylation of vitamin D
Hypercalcaemia - renal stones
Secondary:
Development into tertiary hyperparathyroidism
Osteitis fibrosa cystica
Complications of surgery: hypocalcaemia and recurrent laryngeal nerve palsy
What is the prognosis of hyperparathyroidism?
Primary: surgery is curative for benign disease in most cases
Secondary/tertiary: same prognosis as chronic renal failure
Define acromegaly
Excessive growth hormone release in adults leading to growth of the extremities and other complications usually due to a pituitary adenoma of somatotrophs.
Summarise the aetiology of acromegaly
Usually cause be a pituitary adenoma of the somatotrophs - 90-95% of cases
Hypothalamic tumour causing increased GHRH secretion
Ectopic GH secretion from other tumours
Multiple Endocrine Neoplasia type 1
Summarise the epidemiology of acromegaly
Occurs at 30-50 years old
Rare condition with insidious onset
Equal distribution between men and women
What are the presenting symptoms of acromegaly?
Inisidious onset Excessive sweating Headaches Tiredness Lethargy Visual changes
Caused by increased tissue growth:
No longer fit shoes and rings due to soft tissue growth
Carpal tunnel syndrome (median nerve compression due to soft tissue on wrist)
Arthropathy and joint pain due to cartilage expansion
Features of hypopituitarism if large macroadenomas:
Hypogonadism - secondary amenorrhoea, erectile dysfunction, loss of libido
Hypothyroidism - fatigue
Hypoadrenalism - weight loss
May be associated with hyperprolactinaemia: Galactorrhoea Amenorrhoea Gynaecomastia Low libido
What are the signs on physical examination of acromegaly?
Bitemporal hemianopia Large spade-like hands, thick greasy skin, carpal tunnerl syndrome, premature osteoarthritis Large feet Diabetic retinopathy Macroglossia Prognathism Coarsening of facial features - prominent eyebrow ridge, broad nose bridge, thick lips Barrel chest Kyphosis Hepatosplenomegaly
What are the appropriate investigations for acromegaly?
NOT SERUM GROWTH HORMONE - fluctuates during the day
Serum IGF1 (has long half-life therefore levels stable throughout day) - elevated
Glucose suppression test - lack of suppression of growth hormone following 75g glucose load
MRI brain - shows pituitary adenoma and size
Pituitary function tests: 9am cortisol, free T4 and TSH, LH/FSH, testosterone and prolactin
Thyrotropin-releasing hormone test: TRH may be administered – in acromegalic patients, there is a paradoxical growth hormone response (suppressed in normal people)
What is the management of acromegaly?
Transsphenoidal hypophysectomy or external beam irradiation
Long acting somatostatin analogues eg octeotride
Oral dopamine agonists eg cabergoline, bromocriptine (as GH secreting pituitary tumours express D2 receptors)
GH receptor antagonists (pegvisomant)
What are the possible complications of acromegaly?
Obstructive Sleep Apnoea – soft tissue growth surrounding the upper airway and macroglossia
Hypertension – somatotropin-mediated renal sodium absorption and direct effects of somatotropin and IGF-1 on the vasculature
Cardiomyopathy – cardiomegaly, diabetes mellitus and somatotropin toxicity
Increased risk of cancer – risk of development of colonic polyps
Hyperprolactinaemia – in 30% of cases
Bitemporal hemianopia
Carpal tunnel syndrome
Hypercalcaemia, hyperphosphatemia, renal stones, T2DM
Depression and psychosis (from dopamine agonists – rare)
Complications of surgery: Nasoseptal perforation Hypopituitarism Adenoma recurrence Infection
What is the prognosis of acromegaly?
Prognosis has improved with recent pharmacological and surgical improvements
Life expectancy close to normal
GH and IGF-1 levels can be used to monitor disease control
Good prognosis with early diagnosis and treatment
Physical changes are irreversible
Patient requires lifetime follow-up appointments at a specialist centre (biannual appointments)
High likelihood of recurrence
Define adrenal insufficiency
A condition where the adrenal glands do not produce enough adrenocortical hormones, particularly cortisol and aldosterone, either due to dysfunction or destruction of the gland (primary) or due to lack of stimulatory control from the pituitary/hypothalamus (secondary/tertiary).
Primary adrenal insufficiency is known as Addison’s Disease.
Summarise the aetiology of adrenal insufficiency
Primary adrenal insufficiency (problem is with the adrenal glands):
Autoimmune - most common in Western world - antibodies against the adrenal cortex and/or 21-hydroxylase enzyme.
Infection from TB (most common in developing countries), HIV, disseminated fungal infection
Bilateral metastases
Congenital adrenal hyperplasia - autosomal recessive disease that manifests as an enzyme deficiency
Secondary adrenal insufficiency (problem is with the pituitary not secreting enough ACTH):
Trauma
Panhypopituitarism - due to pituitary macroadenoma or other CNS tumour
Tertiary adrenal insufficiency (problem is with the hypothalamus not secreting enough CRH):
Trauma
CNS tumour
Most common - sudden withdrawal of chronic glucocorticoid treatment or sudden cure of Cushing’s syndrome
Summarise the epidemiology of adrenal insufficiency
The prevalence of hypoaldosteronism is 35-60 cases per million people.
Most cases are iatrogenic (due to sudden cessation of long-term steroid therapy) – primary causes are rare.
