Endocrine Flashcards
What hormones are released from the anterior pituitary?
ACTH
TSH
LH/FSH
GH
What hormones are released from the posterior pituitary?
Prolactin
ADH
What visual disturbance is caused by compression of the optic chiasm?
Bitemporal hemianopia
What are the different types of pituitary tumours?
Non-functional
Functional
Other
What are the effects of functional pituitary tumours?
Prolactin - prolactinoma
GH - acromegaly
ACTH - Cushing’s disease
TSH - TSHoma
Give three examples of ‘other’ pituitary tumours
Craniopharyngioma
Pituitary cancer
Rathke’s cyst
Describe non-functional pituitary tumours
Most common (25%) No hormonal releases Mass effects - visual field defects - headache - stops other pituitary hormones working - eye movement problems due to involvement of cranial nerves --> blurred vision
How should non-functioning pituitary tumours be investigated?
Imaging - MRI
Visual field assessment
Measure pituitary hormones
How should non-functioning pituitary tumours be managed?
Surgery - protection of vision
Radiotherapy
Describe hypopituitarism
Failure of the (anterior) pituitary
Can affect a single hormonal axis or all hormones (panhypopituitarism)
Leads to secondary gonadal/thyroid/adrenal failure
Need multiple hormone replacement
In hypopituitarism, what hormonal replacement therapy should always be started first?
Hydrocortisone
Give some potential causes of hypopituitarism
Tumours Radiotherapy Infarction/haemorrhage (apoplexy) Infiltrate (sarcoid) Trauma Lymphocytic hypophysitis
What are potential causes of high prolactin?
Prolactinomas
Physiological - pregnancy, breast feeding
Drugs that block dopamine
Stalk effect - loss of inhibitory dopamine
Give examples of drugs that block dopamine
Tricyclics
Antiemetics
Antipsychotics
What is a prolactinoma?
Pituitary tumour that secretes prolactin
What are the clinical features of a prolactinoma?
Galactorrhoea Headaches Mass effects Visual field defects Amenorrhoea/erectile dysfunction
Describe the diagnosis of prolactinoma
Serum prolactin (>6000) MRI pituitary Test remaining pituitary function
Describe the treatment of a prolactinoma
Medical:
Dopamine agonist - cabergoline, bromocriptine
Surgical:
VF compromised
Failure of medical therapy
Describe the association of prolactinomas and pregnancy
Pituitary gland get bigger in pregnancy - increase in prolactin production
Dopamine agonists are contraindicated
[Prolactin] is unhelpful
Monitor visual fields if macroprolactinoma
Describe acromegaly
Pituitary tumour secreting growth hormone post puberty
What are the clinical features of acromegaly?
Sweats and headaches Alteration of facial features Increased hand/feet size Visual impairment Cardiomegaly
Describe the diagnosis of acromegaly
Glucose tolerance test (glucose should suppress GH)
Measure IGF-1 (GH stimulates liver to produce IGF-1)
MRI
Describe the management of acromegaly
Surgery - first line to debulk tumour
Drugs:
Somatostatin analogue - octreotide (before and after surgery)
Dopamine agonist
GH receptor antagonist (Pegvisomant)
Radiotherapy - residual tumour/ongoing symptoms
Describe Cushing’s disease
Pituitary tumour secreting ACTH
What are the symptoms of Cushing’s disease?
Weight gain Thin skin Easy bruising Hypertension Osteoporosis
How can Cushing’s disease be diagnosed?
Try to suppress ACTH by dexamethasone suppression therapy
Describe the management of Cushing’s disease
Surgery first line
If fails or inappropriate:
Bilateral adrenalectomy
Medical therapy - metyrapone, ketoconazole
Radiotherapy
Describe TSHoma
Rare pituitary tumour releasing TSH
What TFT results are associated with TSHoma?
High TSH
High fT4
What are the two types of Diabetes Inspidus?
Central
Nephrogenic
What are potential central causes of diabetes insidius?
Idiopathic Trauma Pituitary tumour Pituitary surgery Pregnancy
What are the clinical features of diabetes inspidus?
Polydipsia
Polyuria (>3L/d urine output)
Describe the diagnosis of diabetes inspidus
Try to stimulate the release
Water deprivation test
Assess ability to concentrate urine with ADH (nephrogenic won’t)
What is diabetes inspidus?
ADH deficiency
Describe the treatment of diabetes inspidus
Treat underlying cause
ddAVP (spray, tablets, injection)
What are the layers of the adrenal cortex, and what does each layer produce?
Zona Glomerulosa = aldosterone
Zona Fasciculata = cortisol
Zona Reticularis = androgens
What cells are located in the adrenal medulla, and what do they produce?
Chromograffin cells
Catecholamines
What features are commonly associated with primary aldosteronism (Conn’s syndrome)?
Hypertension
Hypokalaemia
What biochemistry is associated with primary aldosteronism (Conn’s syndrome)?
High aldosterone
Low renin
Very high aldosterone:renin ratio
What medications should be stopped if a patient is thought to have primary aldosteronism (Conn’s syndrome)?
Beta blockers
What medications can be used in patients who have primary aldosteronism (Conn’s syndrome)?
Alpha blockers
Verapamil
Hydralazine
How is primary aldosteronism (Conn’s syndrome) diagnosed?
Saline suppression test
2L of saline over 4 hours (should suppress aldosterone production)
4h aldosterone >470pmol/l = highly suspicious
Describe the management of primary aldosteronism (Conn’s syndrome)
Surgical:
Unilateral laparoscopic adrenalectomy - if adrenal adenoma
Cures hypokalaemia
Cures HTN in 30-70%
Medical: MR antagonist (spironolactone/eplerenone)
What are the clinical features associated with Cushing’s syndrome?
Hirsutism Striae Proximal myopathy Plethora Easy bruising HTN
Describe the diagnosis of Cushing’s syndrome
24h urinary free cortisol
Dexamethasone suppression testing
Late night salivary cortisol (cortisol should be at its lowest levels during the night)
What are the causes of Cushing’s syndrome?
ACTH dependent:
Pituitary adenoma = Cushing’s disease
Ectopic ACTH
Ectopic CRH
ACTH independent:
Adrenal adenoma
Adrenal carcinoma
Nodular hyperplasia
What is the mode of inheritance of congenital adrenal hyperplasia?
Autosomal recessive
Define congenital adrenal hyperplasia
Range of genetic disorders relating to defects in steroidogenic genes
What is the most common gene which is mutated in congenital adrenal hyperplasia?
CYP21 (21 hydroxylase)
What happens to hormone levels in congenital adrenal hyperplasia?
Aldosterone and cortisol not produced
Increased androgen and 17-OH progesterone
What are the effects on males and females in congenital adrenal hyperplasia?
Males: adrenal crisis (hypotension, hyponatraemia), early virilization
Females: ambiguous genitals
What is the management of congenital adrenal hyperplasia?
Mineralocorticoid and glucocorticoid replacement
What are the signs and symptoms of phaechromocytoma?
HTN
Episodes of headaches, palpitations, pallor, sweating
Tremor, anxiety, N&V, chest/adbo pain
Crisis last ~15 mins
Generally otherwise well
What are the causes of phaechromocytoma?
Genetics - 25%
Malignancy - 15-20%
Benign - 80-85%
What genetics are associated with phaechromocytoma?
MEN, VHL, SDHB & SDHD mutations,
Neurofibromatosis
Describe the pre-operative treatment of phaechromocytoma
Alpha blockers initially
(Phenoxybenzamine/doxazosin)
Aim for SBP <120mmHg
Beta blockers if tachycardic
Labetolol, bisopropol
Encourage salt intake (maintain fluid status)
Define adrenal insufficiency
Inadequate adrenocortical function
What are the clinical features of adrenal insufficiency?
Anorexia, weight loss Fatigue, lethargy Dizziness, hypotension Abdo pain, vomiting, diarrhoea Skin pigmentation
What is the ‘suspicious biochemistry’ associated with adrenal insufficiency?
Low Na
High K
Hypoglycaemia
What test can be used to assess whether a patient has adrenal insufficiency?
Short SynACTHen test
Measure plasma cortisol levels before and 30m after IV ACTH injection
Normal: baseline >250nmol/L, post ACTH >480nmol/L
What ACTH, renin and aldosterone levels are associated with adrenal insufficiency?
High ACTH
High Renin
Low Aldosterone
Give three functions of Ca
Muscle contraction Bone growth and remodelling Second messenger signalling Stabilising of membranes Enzyme co-factor Secretion of hormones (insulin)
What is the normal total calcium range?
2.2-2.6mmol/L
Describe the position of the parathyroid glands
Usually 4 glands on the posterior aspect of the thyroid gland
2 at superior poles; 2 at inferior poles
Supplied by the inferior thyroid artery
10% of people have ectopic parathyroid glands
What effect does PTH have on blood calcium levels?
Increases
What are the actions of PTH in the kidneys?
Reabsorption of calcium at DCT
Internalisation of Na/PO4- co-transporter at PCT (hypophosphataemia and hypercalcaemia)
Inhibits N/H exchanger –> bicarbonate wasting (mild acidosis)
What are the actions of PTH on the bones?
Continuous PTH = increased number and activity of osteoclasts
Intermittent PTH = increased number of osteoblasts
What are the actions of PTH in the gut?
Stimulates the synthesis of active form of VIT D in the kidney (1,25-dihydroxycholecalciferol) –> increases Ca absorption in gut
Where is PTH stored?
Chief cells in parathyroid gland
What controls the secretion of PTH?
Ca Sensing Receptors (CaSR)
Where are CaSR located?
Parathyroid gland
Thyroid
Kidney
Describe what happens when CaSR are activated in the parathyroid gland
Rising Ca –> activates CaSR
Inhibits translation of PTH gene
PTH secretion inhibited
(Rising Ca –> activates calcium sensing proteases –> degrade PTH)
What familial condition is associated with loss of function of the CaSR?
Familial hypocalciruric hypercalcaemia
Describe what happens when CaSR are activated in the kidney
Increases urinary Ca and Mg excretion
Increases Na, K, Cl excretion
Describe what happens when CaSR are activated in the thyroid
Stimulates the release of calcitonin from C cells –> lowers serum Ca
Describe the process by which Vit D is activated
Cholecalciferol (UV light) and Ergocalciferol (diet) are inactivated
Hydroxylated in liver to 25-hydroxycholecalciferol (storage form)
Hydroxylated in kidneys to 1,25-dihydroxycholecalciferol (active form)
Give three actions of Vit D
Increases calcium and phosphate absorption from gut
Bone mineralisation and mobiles Ca stores
Immunomodulation
Increases bone strength
Reduces insulin resistance
Interaction with RAAS
Give the assay results associated with 25-hydroxycholecalciferol
<15nmol/l = severe deficiency 15-30nmol/l = deficiency >50nmom/l = adequate
What is the normal range for 1,25-dihydroxycholecalciferol?
50-125pmol/L
If a patient has a raised serum Ca, what should always be measured?
PTH
When do symptoms of hypercalcaemia generally arise?
Serum Ca >3mmol/L
Give some symptoms associated with hypercalcaemia
Confusion, depression, fatigue, coma
Shortening of QTc, bradycardia, HTN
Polyuria, nephrogenic DI, stones, nephrocalcinosis
Anorexia, constipation, nausea, pancreatitis
Muscle weakness, bone pain, osteoporosis
Give DDx if Calcium and PTH are both raised?
Parathyroid overactivity
Familial hypocalciuric hypercalcaemia
Lithium
Give DDx if Calcium is raised and PTH is normal?
Parathyroid overactivity
Familial hypocalciuric hypercalcaemia
Lithium
Give DDx if Calcium is raised and PTH is undetectable?
Malignancy
Drugs (thiazide, lithium, calcium supplements)
Granulomatous disease
What investigations are needed if a patient has hypercalcaemia?
Hx and examination CXR (signs of malignancy, hilar lymphadenopathy - signs of sarcoidosis) FBC, ESR TFTs Myeloma screen Short SynACTHen test Vit D
What are the ways in which malignancies can cause hypercalcaemia?
Osteolytic metastases and myeloma
Tumour secretes PTHrP
Tumour produces 1,25-dihydroxycholecalciferol
What tumours are most likely to secrete PTHrP?
Squamous cell lung cancer
Oesophageal cancer
Renal cell carcinoma
Breast cancer
What type of tumour is most likely to produce 1,25-dihydroxycholecalciferol?
Lymphoma (activated macrophages)
Give examples of conditions which can produce endogenous 1,25-dihydoxycholecalciferol
Lymphoma
Sarcoid
Wegner’s granulomatosis
(usually responds to steroids)
Why does adrenal insufficiency cause hypercalcaemia?
Increases PCT Ca reabsorption
Increases bone resorption
Describe Milk-Alkali syndrome
Hypercalcaemia
Metabolic acidosis
Renal insufficiency
(ingestion of calcium and antacids - rare with PPI)
What is the management of PTH independent hypercalcaemia?
Stop offending/contributing medications
Rehydrate (3-4L normal saline in 24h)
±loop diuretics - promotes calciuria
Bisphosphonates (inhibits bone reabsorption)
Steroids (haematological malignancy, vit D intoxication, granulomatous disease)
Who is most likely to have primary hyperparathyroidism?
Postmenopausal women
What are the causes of primary hyperparathyroidism?
85% isolated parathyroid adenoma
14% parathyroid hyperplasia
<1% parathyroid carcinoma
What end organ damage is associated with primary hyperparathyroidism?
Bone:
Osteoporosis
Bone cysts, subperiosteal resorption
Brown tumours (collections of osteoclasts, mineralised bone and fibrous tissue)
Kidney:
Renal calculi
Nephrocalcinosis - calcium deposits in kidney
Renal impairment
Pancreatitis
What investigations should be arranged to confirm diagnosis of primary hyperparathyroidism?
DHx U&Es PTH Urine calcium:creatinine ratio Vit D
What investigations should be arranged to assess end organ damage in primary hyperparathyroidism?
DEXA
Renal USS
When should MEN-1/2 be considered as a potential cause of primary hyperparathyroidism?
<40yr
Hx of hyperparathyroidism in 1st degree relative
What investigations are needed if surgery is indicated in the management of primary hyperparathyroidims?
Sestamibi - radio labelled isotope –> taken up by parathyroid gland
Neck USS
What are the indications for parathyroidectomy?
Calcium >3mmol/L
Hypercalciuria
Osteoporosis
Renal stones
What complications are associated with parathyroidectomy?
Vocal cord paresis, haematoma causing tracheal compression
Transient hypocalcaemia,
“Hungry bones”
If someone has no-end organ damage or is unfit for surgery for management of their primary hyperparathyroidism, what surveillance should they have?
Annual bone profile, renal function and urinary calcium
DEXA and renal USS every 3y
Describe the medical RRx for primary hyperparathyroidism
Only if not fit for surgery
Bisphosphonates - preserve bone mass but little effect on calcium
Calcium sensing agonists (cinacalcet)
Reduces serum calcium but doesn’t prevent end-organ damage
Give three causes of vitamin D deficiency
Poor sunlight exposure Malabsorption Gastrectomy Enzyme inducing drugs - anticonvulsants Renal disease
Define osteomalacia
Failure to ossify bones in adulthood as a result of Vit D deficiency leading to hypo-mineralisation of trabecular and cortical bone
How does osteomalacia present?
Bone pain
Proximal myopathy
Hypocalcaemia
What biochemistry results are suggestive of osteomalacia?
Low calcium Low phosphate High Alk Phos Low Vit D Elevated PTH
What radiological appearances are associated with osteomalacia?
Looser zone - pseudo-fractures commonly occur in femur/pelvis
Osteopenia - areas of low bone density
How can Vit D deficiency be managed?
Cholecalciferol (D3) = restores body stored, corrects metabolic disturbances
Alfacalidol (active Vit D) - in renal impairment, heal bony abnormalities
Define diabetes
A metabolic disorder of multiple aetiology characterised by chronic hyperglycaemia with disturbance of carbohydrate, protein and fat metabolism resulting in defects in insulin secretion, insulin action or both
Describe and explain the symptoms of diabetes
Glycosuria –> depletion of energy stores
(Tired, weak, weight loss, difficulty concentrating, irritability)
Glycosuria –> osmotic diuresis
(Polyuria, polydipsia, thirst, dry mucous membranes, reduced skin turgor, postural hypotension)
Glucose shifts –> swollen ocular lenses
(Blurred vision)
Describe and explain the presentation of insulin deficiency
Ketone production (N&V, abdo pain, heavy/rapid breathing, acetone breath, drowsiness, coma)
Depletion of energy stores
(Weakness, polyphagia, weight loss, growth retardation in young)
Complications (T2DM)
(Microvascular, macrovascular, neuropathy, infection)
What are the diagnostic values for diabetes in a fasting glucose test?
Normal: <7.0
Diabetes >7.0
What are the diagnostic values for diabetes in a OGTT?
Normal: <7.8
IGT: 7.8-11.0
Diabetes: >11.1
What HbA1c value corresponds to diabetes?
6.5% (48mmol/L)
Describe T1DM
Chronic, progressive metabolic disorder characterised by hyperglycaemia and the absence of insulin secretion due to autoimmune destruction of beta cells in the Islets of Langerhans
Describe T2DM
Chronic, progressive metabolic disorder characterised by hyperglycaemia, insulin resistance and relative impairment of insulin deficiency
How is MODY inherited?
Autosomal dominant
How many genes cause MODY, and what is the most common?
6 genes
HNF1-alpha 70%
What are the three main features of MODY?
Often <25y at onset
Runs in families - autosomal dominant
Managed by diet, OHAs, insulin
Define gestational diabetes
Carbohydrate intolerance with onset, or diagnosis, during pregnancy
What risk factors are associated with gestational diabetes?
High BMI
Previous macrosomic baby/gestational DM
FHx of diabetes
Who should be tested for gestational diagnosis, when and what is the criteria?
Women with risk factors
OGTT at 24-28 weeks
Fasting venous plasma glucose >/= 5.1mmol/L OR
1 hour value >/= 10.0mmol/L OR
Two hours after >/= 8.5mmol/L
Give potential causes of secondary DM
Disorders of exocrine pancreas (pancreatitis, carcinoma, CF, haemochromatosis)
Endocrinopathies (Acromegaly, Cushing’s, phaechromocytoma)
Drug therapies (Immunosuppressive agents, anti-psychotics)
Under fasting conditions, what is the basal secretion of insulin per hour?
40ug/h
Describe the release of insulin
1st phase: stored insulin is released immediately due to increased plasma glucose levels
2nd phase: blood insulin levels starts to fall, the pancreas produces more insulin
Give an example of a short/rapid (bolus) insulin
Novorapid
Give an example of intermediate/long (basal) insulin
Determir
Degludec
Glargine
Give and example of a mixed insulin
Novomix 30
Humalog Mix 25/50
What is Whipple’s triad in regard to hypoglycaemia?
- Symptom of low blood glucose
- Measure low plasma glucose
- Symptoms improve with glucose
At what concentration of blood glucose are counter-regulatory hormones released? What hormones are they? What is the effect?
3.8mmol/L
Glucagon and adrenaline
Sweating, palpitations, shaking, nausea, anxiety
What what blood glucose concentration is cognitive function impaired?
2.5-2.8mmol/L
How is mild hypoglycaemia treated in hospital?
Give 15-20g of quick acting carbohydrate
Test blood glucose after 15mins
If <4mmol/L repeat up to 3x
How is moderate hypoglycaemia treated in hospital?
If capable and cooperative, 15-20g of quick acting carbohydrate
If not, 1.5-2 tubes GlucoGel or 1mg Glucagon IM
Test blood glucose levels after 15mins
If <4mmol/L repeat up to 3 times
How is severe hypoglycaemia treated in hospital?
Check ABC Stop IV insulin Give IV glucose over 10 mins Test blood glucose after 10 mins If <4mmol/L repeat
How often does a person with diabetes need to check their blood glucose levels whilst driving?
Every 2 hours
What are the three aspects of DKA?
- Metabolic acidosis (pH <7.3)
- Plasma glucose (>13.9mmol/L)
- Urinary/plasma ketones (++ on urine/ >3mmol/L in plasma)
What are some of the symptoms of DKA?
Breathlessness - Kussmaul's breathing Abdominal pain Leg cramps N&V Confusion
What are some of the precipitants of ketoacidosis?
New onset DM Insulin omission Acute illness Steroids Infections
What losses are associated with DKA?
Water: 6-8L (100ml/kg)
Sodium: 500-1000mmol/L
Chloride: 350mmol/L
Potassium: 300-1000ml/L
Describe the management of DKA
Treat the precipitant
Fluids
Potassium replacement
Insulin - with glucose once the blood glucose levels starts to fall
How high are the blood glucose levels in HHS?
> 30mmol/L
What are precipitating factors of HHS?
Infection
Poor compliance
Drugs
Describe the management of HHS
Treat the precipitant
Fluids
0.9% saline
Rate of Na fall should not exceed 10mmol/24hr
Insulin
Rate of fall no more than 5mmol/L/hr
Other
LMWH
Foot protection
