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.
What are the presenting symptoms of adrenal insufficiency?
Chronic symptoms: Fatigue Weight loss Weakness Dizziness Anorexia D&V Abdominal pain
Acute presentation (Addisonian crisis): Acute adrenal insufficiency, major haemodynamic collapse Fever Back, abdominal and leg pain Vomiting, diarrhoea, dehydration Syncope Altered mental state NOTE: Addisonian crisis may be precipitated by stress (infection, surgery)
Symptoms specific to primary adrenal insufficiency: Due to decreased aldosterone: Hyponatreamia Hyperkalaemia Hypotension Craving salty food
Due to decreased cortisol:
Hypoglycaemia
Hyperpigmentation in the mouth, hair and skin
Autoimmune vitiligo
What are the signs on physical examination of adrenal insufficiency?
Hypotension and postural hypotension
Pigmentation: noticeable on buccal mucosa, scars, skin creases, nails, pressure points
Associated autoimmune conditions
Congenital adrenal hyperplasia:
Loss of body hair in women (due to androgen deficiency)
Hirsutism in women
Enlarged phallus in male children
Addisonian Crisis Signs: Hypotensive shock Tachycardia Pale Cold Clamminess Oliguria
What are the appropriate investigations for adrenal insufficiency?
Morning serum cortisol at 9am - normally would be high. Low < 100 nmol/L is diagnostic of adrenal insufficiency
Serum ACTH - if high then patient has Addison’s. If low, then secondary or tertiary cause.
Short acting synacthen test - give 250mg synacthen (exogenous ACTH) and measure cortisol response. If cortisol still low - primary adrenal insufficiency.
Abdominal CT - look for adrenal mets
CXR and tuberculin test - check for infection as cause of Addison’s
HIV test
Serum anti-adrenal antibodies
Serum measurements of Na, K, urea, Ca and eosinophilia to support diagnosis
Serum aldosterone and renin measurement (if aldosterone low and renin high - Addison’s)
FBC: neutrophilia - infective cause (also measure CRP/ESR here)
What is the management of adrenal insufficiency?
Addison’s crisis:
IV fluids and IV hydrocortisone 50-100mg
50mg bolus of hydrocortisone ever 8 hours until able to take oral meds
50ml dextrose 50% to treat hypoglycaemia
Primary adrenal insufficiency:
Hydrocortisone to replace cortisol
Fludrocortisone to replace aldosterone
Increase dose if undergoing surgery, febrile or severe illness or after trauma
What are the possible complications of adrenal insufficiency?
HYPERKALAEMIA AND DEATH DURING A CRISIS Long-term glucocorticoid treatment: Osteoporosis - regular bone density measurements are performed Iatrogenic Cushing’s syndrome Treatment-related hypertension.
What is the prognosis of adrenal insufficiency?
Adrenal function rarely recovers, but patients do have a normal life expectancy if treated
Autoimmune Polyendocrine Syndrome - Type 1: Autosomal recessive disorder caused by mutations in the AIRE gene
Addison’s disease
Chronic mucocutaneous candidiasis
Hypoparathyroidism
Type 2/Schmidt's Syndrome: Addison's disease Type 1 Diabetes Hypothyroidism Hypogonadism
Define Cushing’s syndrome
Syndrome associated with chronic inappropriate elevation of free circulating cortisol.
Cushing’s disease = excess cortisol due to pituitary adenoma releasing too much ACTH
Summarise the aetiology of Cushing’s syndrome
Most common cause = chronic use of glucocorticoids medication
Cushing’s disease - pituitary adenoma secreting excess ACTH
Ectopic ACTH production from small cell lung cancer
Adrenal adenoma or carcinoma secreting excess cortisol
Summarise the epidemiology of Cushing’s syndrome
Rare More common in women Can occur at any age Diagnosis usually between 20 and 50y/o Exogenous corticosteroid use is most common cause
What are the presenting symptoms of Cushing’s syndrome?
Increasing weight Fatigue Muscle weakness Myalgia Thin skin Easy bruising Poor wound healing Fractures Hirsutism Acne Frontal balding Oligomenorrhoea/amenorrhoea Depression or psychosis Polyuria and polydipsia
What are the signs on physical examination of Cushing’s syndrome?
Moon face Facial plethora Interscapular fat pad Proximal muscle weakness Thin skin Bruises Central obesity Purple striae on abdomen/breast/thighs Kyphosis (due to vertebral fracture) Poorly healing wounds Hirsutism, acne, frontal balding HYPERTENSION Ankle oedema (salt and water retention from the MR effect of excess cortisol) Pigmentation in ACTH dependent cases Increased blood glucose
What are the appropriate investigations in Cushing’s syndrome?
24hr urinary free cortisol - high at all times
Low dose overnight dexamethasone suppression test - give 1mg dexamethasone at midnight, if Cushing’s present then cortisol will still be raised in morning
Serum ACTH - high if Cushing’s disease or ectopic ACTH, low if adrenal tumour
Pituitary MRI - show pituitary adenoma if Cushing’s disease
Abdo CT - look for source of ectopic ACTH
CT adrenals - look for adrenal carcinoma or adenoma
BM - high glucose
If lung cancer suspected: CXR, sputum cytology, bronchoscopy, CT scan, radiolabelled octreotide scans can detect carcinoid tumours
Low dose dexamethasone suppression test (LDDST): 0.5 mg dexamethasone orally ever 6 hours for 48 hrs. In Cushing’s syndrome, serum cortisol measured 48 hrs after the first dose of dexamethasone fails to suppress below 50 nmol/L
What is the management of Cushing’s syndrome?
Depends on cause
Due to exogenous glucocorticoid: slowly decrease dose to prevent Addisonian crisis
Due to pituitary adenoma: transsphenoidal hypophysectomy
Adrenal adenoma/carcinoma – surgical removal of tumour
Ectopic ACTH – treatment directed at the tumour
Adrenal steroid inhibitors if ectopic ACTH or adrenal tumour eg KETOCONAZOLE, METYRAPONE
Treat osteoporosis
Physiotherapy for muscle weakness
What are the possible complications of Cushing’s disease?
Hypertension
Osteoporosis
Diabetes
Increased susceptibility to infections
Complications of surgery: CSF leakage Meningitis Sphenoid sinusitis Hypopituitarism
Complications of radiotherapy:
Hypopituitarism
Radionecrosis
Increased risk of second intracranial tumours and stroke
Addisonian crisis due to stopping exogenous glucocorticoids
Summarise the prognosis of Cushing’s syndrome
Untreated 5-year survival = 50%
Low survival mainly due to cardiovascular disease caused by Cushing’s
When cortisol levels normalised, similar life expectancy to general population
Depression persists for many years following treatment
Define SIADH
An inappropriate amount of ADH is secreted for the blood osmolality and is secreted without the usual triggers.
It is characterised by hyponatraemia, concentrated urine, and a euvolaemic state.
Explain the aetiology of SIADH
Surgery Ectopic ADH secretion - small cell lung cancer paraneoplastic syndrome Head trauma Sepsis Lung abscess Lung pathology eg COPD, pneumonia Stroke/neurological disease Anti-epileptics
Summarise the epidemiology of SIADH
Hyponatraemia is the MOST COMMON electrolyte imbalance seen in hospital
< 50% of severe hyponatraemia is caused by SIADH
What are the presenting symptoms of SIADH?
Headaches Nausea Vomiting Tremor Muscle cramps
Severe hyponatreamia leads to cerebral oedema causing:
Confusion
Mood swings
Hallucinations
What are the signs on physical examination of SIADH?
MILD hyponatraemia – no signs
SEVERE hyponatraemia – Reduced reflexes (extensor plantar reflexes)
Signs of underlying cause
What are the appropriate investigations for SIADH?
Plasma osmolality - decreased
Plasma sodium - decreased
Urine osmolality - increased
Urine sodium - increased
Rule out other causes as SIADH is diagnosis of exclusion:
Glucose, serum protein and lipids: to rule out pseudohyponatraemia
Free T4 and TSH – hypothyroidism can cause hyponatraemia
Short synacthen test – adrenal insufficiency can cause hyponatraemia
Creatinine - check renal function
What is the management of SIADH?
Fluid restriction
High salt diet
In severe cases - IV hypertonic sodium chloride 1.8% given SLOWLY to avoid central pontine myelinolysis
Demeclocycline (ADH receptor antagonist) if resistant
What are the possible complications of SIADH?
Hyponatraemia
Cerebral oedema - seizure, coma, death
Complication of treatment: Central pontine myelinolysis - occurs with rapid correction of hyponatraemia. Characterised by: Quadriparesis Respiratory arrest Fits
Summarise the prognosis of SIADH
If cause identified and treated, SIADH is resolved
Hyponatraemia is associated with a HIGH MORBIDITY and MORTALITY
50% mortality with central pontine myelinolysis
Define diabetes insipidus
Polydipsia and hypotonic polyuria due to an absence of or lack of response to ADH.
Summarise the aetiology of diabetes insipidus
Central diabetes insipidus: There is not enough ADH due to either the hypothalamus not producing it, or the pituitary being unable to release it Head trauma Head surgery Pituitary tumour Ischaemic encephalopathy Iatrogenic
Nephrogenic diabetes insipidus: Kidneys are unable to respond to ADH Genetic disorder causing ineffective vasopressin receptors or aquaporin proteins Lithium Hypercalcaemia Hypokalaemia Demeclocycline PCOS
Summarise the epidemiology of diabetes insipidus
Uncommon
Median age of onset is 24 years old
What are the presenting symptoms of diabetes insipidus?
Polyuria Polydipsia Dehydration Nausea Fatigue Confusion Poor concentration Nocturia Bed wetting and sleep disturbance in children
What are the signs on physical examination of diabetes insipidus?
Urine output > 3 L/day
If fluid intake < fluid output, signs of dehydration will be present (e.g. tachycardia, reduced tissue turgor, postural hypotension, dry mucous membranes)
Signs related to the cause (e.g. visual defect due to pituitary tumour)
What are the appropriate investigations of diabetes insipidus?
Plasma osmolality - increased. Normal if psychogenic polydipsia Plasma sodium - increased Urine osmolality - decreased Urine sodium - decreased Urine specific gravity - low Serum ADH - low if central DI
Water deprivation test:
No drinking for 3 hours:
If psychogenic polydipsia, urine osmolality will increase
If urine osmolality stays same, CENTRAL OR NEPHROGENIC DI
Give desmopression (ADH analogue):
If central diabetes insipidus, urine osmolality increases
If nephrogenic diabetes insipidus, urine osmolality stays the same
What is the management of diabetes insipidus?
Central:
Desmopressin
Nephrogenic:
Thiazide diuretic, potassium sparing diuretic, salt restriction, adequate hydration
IV FLUIDS TO CORRECT HYPERNATREAMIA
What are the possible complications of diabetes insipidus?
Hypernatraemia
Thrombosis (increased risk in hypernatraemia and dehydration combined)
Bladder and renal dysfunction (due to excessive urinary volume)
Iatrogenic hyponatraemia due to DDAVP and IV fluid replacement
What is the prognosis of diabetes insipidus?
Cranial DI may be transient following head trauma
It may be cured by removing the cause (e.g. drug discontinuation, tumour resection)
Define prolactinoma
A benign pituitary adenoma of the lactotrophs in the anterior pituitary, causing excessive prolactin secretion.
Summarise the aetiology of prolactinoma
Largely unknown
Mostly occur sporadically
Multiple Endocrine Neoplasia Type 1 - 20% of these patients develop prolactinoma. These prolactinomas are more aggressive
Familial Isolated Pituitary Adenoma
Summarise the epidemiology of prolactinoma
Prolactinoma are the most common type of pituitary adenoma - approximately 40% of them
More frequent in women during child-bearing years
Peak incidence in 20s-30s
After 50s, prevalence is similar in men and women
What are the presenting symptoms of prolactinoma?
Headache Bitemporal hemianopia Decreased libido Infertility Symptoms of hypopituitarism
Women: Galactorrhoea Vaginal dryness leading to dyspareunia Secondary amenorrhoea or oligomenorrhoea Acne Hirsutism
Men:
Gynaecomastia
Erectile dysfunction
What are the signs on physical examination of prolactinoma?
Signs of hypopituitarism
Men:
Gynaecomastia
Females:
Brittle bones/easy fractures/premature osteoporosis
What are the appropriate investigations for prolactinoma?
Pregnancy test
Serum prolactin - raised
Serum thyrotropin releasing hormone may be high
Serum FSH and LH - low
TFTs: hypothyroidism causes high TRH which can stimulate prolactin release
Serum prolactin level > 5000 mU/L suggests true prolactinoma
MRI brain - visualise the adenoma
What is the management of a prolactinoma?
Asymptomatic microprolactinoma - watchful waiting
Medical:
Dopamine agonists eg cabergoline, bromocriptine
Transsphenoidal hypophysectomy to remove adenoma
If non-responsive, radiation can be used
Oestrogens for microprolactinomas in females, where the primary complaint is not infertility or galactorrhoea
Why would you chose cabergoline over bromocriptine?
Cabergoline is taken once or twice a week and bromocriptine is taken once a day
Bromocriptine has more side effects
What are the complications of prolactinoma?
Bitemporal hemianopia Infertility Osteoporosis Erectile dysfunction Headache Pituitary apoplexy CSF rhinorrhoea
What is the prognosis of prolactinoma?
Dopamine agonists will result in prolactin normalisation, tumour shrinkage or disappearance, and rapid visual improvement
Microprolactinomas will spontaneously resolve in about 1/3 cases.
Dopamine agonist withdrawal is usually attempted after about 2-3 years if prolactin levels have normalised and tumour volume is reduced.
High rates of recurrence.
Define hypopituitarism
Deficiency in one or more of the anterior pituitary hormones. Panhypopituitarism is when all the pituitary hormones are decreased.
Summarise the aetiology of hypopituitarism
Pituitary adenoma causing compression
Craniopharyngioma causing compression - in children
Pituitary apoplexy due to hemorrhage of vessels supplying pituitary adenoma
Sheehan’s syndrome causing pituitary ischaemia and necrosis following post-partum blood loss
Pituitary radiation
Pituitary surgery
Head trauma
Empty sella syndrome causes CSF to fill sella and pituitary atrophy
Infiltrative disease – sarcoidosis, haemochromatosis, Langerhans’s cell histiocytosis
Infection – meningitis, encephalitis
Summarise the epidemiology of hypopituitarism
Rare
Annual incidence = 4 in 100,000
Associated with 1.8 fold higher mortality
What are the presenting symptoms and signs on physical examination of hypopituitarism?
Headaches
Bitemporal hemianopia
Other symptoms depend on deficient hormones: GH deficient: Short stature (children) Low mood Fatigue Reduced exercise capacity and muscle strength Increased abdominal fat mass (adults) Delayed puberty Low bone density
LH/FSH deficient:
Delayed puberty
Loss of secondary sexual hair
Infertility
Decreased libido
Breast atrophy/menstrual irregularities/dyspareunia (females)
Gynaecomastia/small and soft testes (males)
ACTH deficient: signs and symptoms of adrenal insufficiency Weight loss Orthostatic hypotension Weakness and lethargy Tachycardia Low blood sugar and sodium
TSH deficient: signs and symptoms of hypothyroidism Weight gain Constipation Bradycardia Fatigue Hypotension Slow relaxing reflexes Cold intolerance
Prolactin deficient: absence of lactation (not usually noticed clinically) and amenorrhea
What are the appropriate investigations for hypopituitarism?
Pituitary function tests Basal tests: 9am cortisol and serum ACTH Serum LH/FSH, testosterone/oestrogen Serum IGF-1 Serum prolactin Serum free T4/TSH
Dynamic tests: insulin-induced hypoglycaemia (should cause a rise in GH and cortisol if normal)
Short synacthen test (adrenal insufficiency)
MRI/CT of brain
Visual field testing
What is the management of hypopituitarism?
Transsphenoidal resection if tumour
Pituitary hormone replacement
If prolactinoma: dopamine agonists eg cabergoline and bromocriptine
Low ACTH - hydrocortisone
Low TSH - levothyroxine
Low FSH/LH - testosterone or combined oestrogen and progesterone
Low GH - growth hormone
What are the possible complications of hypopituitarism?
Infertility Addisonian crisis Hypoglycaemia Myxoedema coma Infertility Osteoporosis Dwarfism (children) Bitemporal hemianopia Hydrocephalus Temporal lobe epilepsy
Summarise the prognosis of hypopituitarism
1.8 fold higher mortality than age and sex matched population
CVS and cerebrovascular death rates higher
Good prognosis with lifelong treatment
Define hypothyroidism
The clinical syndrome resulting from low T3 and T4 which may be primary or secondary
Summarise the aetiology of hypothyroidism
Primary hypothyroidism - 95% of cases
Iodine deficiency - most common cause in developing countries
Hashimoto Thyroiditis - most common cause in developed countries, autoimmune destruction of thyroid gland, associated with HLA-DR3
De Quervain thyroiditis - self-limiting, following flu-like illness
Post-partum hypothyroidism
Congenital hypothyroidism - agenesis or dysgenesis of the thyroid
Drugs - antithyroid, lithium, amiodorone
Iatrogenic - radioiodine or thyroidectomy
Secondary hypothyroidism:
Pituitary adenoma
Tertiary hypothyroidism:
Hypothalamic trauma
Hypothalamic tumour
Summarise the epidemiology of hypothyroidism
More common in women
Prevalence increases with age
More common in white patients
What are the presenting symptoms of hypothyroidism?
Cold intolerance Fatigue Constipation Weakness Weight gain with loss of appetite Puffy face Lump in neck Menorrhagia Low libido Oligomenorrhoea Dry skin Hair loss - loss of outer third of eyebrow Brittle hair and nails Hoarse voice Mental slowness Depression Cramps
What are the signs and symptoms of myxoedema coma?
Confusion Altered consciousness Hypothermia Hypoventilation Heart failure Hyponatraemia Bradycardia Hypotension
What are the signs of hypothyroidism on physical examination?
Bradycardia Cold, dry skin Brittle hair and nails Loss of outer third of the eyebrows Pretibial myxoedema Periorbital oedema Non-pitting oedema Puffy face Goitre Slow relaxation of reflexes Thick tongue
What are the appropriate investigations for hypothyroidism?
Serum T3 and T4 - low
Serum TSH - high if primary cause, low if secondary or tertiary cause
Anti-thyroid peroxidase - positive if Hashimoto thyroiditis
Anti-thyroglobulin - positive if Hashimoto thyroiditis
MRI - if suspect secondary or tertiary to look for tumour
What is the management of hypothyroidism?
Levothyroxine (25-200 mcg/day) - dose depending on TFTs and clinical picture
Rule out underlying adrenal insufficiency before starting thyroid hormone replacement as it can lead to Addisonian crisis
Myxoedema coma: IV T3/T4 Oxygen Rewarming Rehydration IV hydrocortisone Treat underlying cause (e.g. infection)
What are the possible complications of hypothyroidism?
Myxoedema coma Myxoedema madness (psychosis with delusions and hallucinations or dementia)
Overtreatment:
AF
Osteoporosis
What is the prognosis of hypothyroidism?
Lifelong levothyroxine is required
Excellent prognosis with thyroid hormone replacement
Resistant hypothyroidism due to non-adherence
Myxoedema coma mortality = 80%
