Endocrinology Flashcards
Hormones released from the anterior pituitary gland
LH FSH TSH Prolactin ACTH GH
Hormones released from the posterior pituitary gland
Vasopressin/ADH
Oxytocin
Pathophysiology of T1DM
Autoimmune destruction of pancreatic beta cells in the islets of Langerhans
Pathophysiology of T2DM
Decreased insulin secretion and increased insulin resistance peripherally
Maturity onset diabetes of the young is what kind of diabetes
Type 2
Rare autosomal dominant
What is an impaired glucose tolerance?
Fasting <7mmol/L (otherwise this is diabetes)
2 hour glucose >7.8mmol/L but <11.1mmol/L
What is impaired fasting glucose?
Fasting >6.1 but <7mmol/L
What is metabolic syndrome/ syndrome X?
Central obesity (BMI>30) BP 130/85 fasting glucose >5.6 T2DM Various forms of hyperlipidaemia
Diagnosis of T2DM
Symptoms of hyperglycaemia and raised venous glucose detected once- fasting >7mmol/L or random >11.1
OR
Raised venous glucose on two separate occassions
HbA1c >48mmol/mol
Symptoms of hyperglycaemia
Polyuria, polydipsia, unexplained weight loss, visual blurring, genital thrush, lethargy
Clinical features of hypoglycaemia
Autonomic- sweating, anxiety, hunger, tremor, palpitations, dizziness
Neuroglycopenic- confusion, drowsiness, visual trouble, seizures, coma, rarely focal neurology, personality change, restlessness
Definition of hypoglycaemia
<4mmol/L plasma glucose
Fasting hypoglycaemia aetiology
Insulin or sulphonylurea treatment in a diabetic is the top cause Non-diabetics EXogenous drugs- insulin, oral hypoglycaemics Pituitary insufficicency Liver failure Addison's disease Islet cell tumours- insulinoma Neoplasms
Effect of active T3 and T4 in the body
Increase cell metabolism
Increase catecholamine effects
Why should TFTs be taken at the same time each day?
Trough at 2pm and higher in the night- variation throughout
Sick euthyroid tests
All low- should recover after illness, retest once recovered
What are anti-TPO antibodies and when are they raised?
Anti-thyroid peroxidase antibodies
Raised in autoimmune disease- Hashimoto’s or Graves’ disease
If positive in Graves then there is a chance of hypothyroidism following
TSH receptor antibody present in
Graves’ disease
Serum thyroglobulin useful as
A tumour marker to monitor the treatment of carcinoma
Clinical features of thyrotoxicosis
Symptoms- diarrhoea, weight loss, increased appetite, over-active, sweaty, heat intolerant, palpitations, tremor, irritability, labile emotions, oligomenorrhoea +/- infertility
Rarely psychosis, chorea, panic, itch, alopecia, urticaria
Signs- tachycardic, irregular pulse, warm moist skin, fine tremor, palmar erythema, thin hair, lid lag, lid retraction
Examination- goitre, thyroid nodules, bruit
Signs specific to Graves’ disease
Exophthalmos, ophthalmoplegia, proptosis
Pretibial myxoedema
Thyroid acropatchy
Tests in thyrotoxicosis
May be mild normocytic anaemia Mild neutropenia Raised T3 and T4 Low TSH Raised ESR Raised Ca Raised LFTs Thyroid autoantibodies- TPO and TSH receptor antibody
Treatment of thyrotoxicosis
Symptomatic control with beta blockers- propanolol
Anti-thyroid hormone- carbimazole ‘block’
Levothyroxine ‘replace’
Radioiodine if become hypothyroid post-treatment, though beware thyroid storm
Thyroidectomy
Causes of thyroid goitre
Physiological
Graves’ disease
Hashimoto’s thyroiditis
Subacute de Quervain’s thyroiditis (self-limiting post-illness)
Clinical features of hypothyroidism
Symptoms- tiredness, lethargic, decreased mood, cold intolerance, weight gain, constipation, menorrhagia, hoarse voice, decreased memory/ cognition, dementia, myalgia, cramps, weakness
Signs- bradycardic, reflexes relax slowly, ataxia, dry thin hair/ skin, yawning, drowsiness, coma, cold hands, ascites, round puffy face, defeated demeanour, immobile,
Aetiology of hypothyroidism
Primary atrophic hypothyroidism
Hashimoto’s thyroiditis-goitre
Drug induced- amiodarone, anti-thyroid, lithium, iodine
Secondary due to hypopituitarism
What is myxoedema coma?
The ultimate hypothyroid state before death
Risks from subclinical hyperthyroidism
AF and osteoporosis
Actions of parathyroid hormone
Increasing osteoclast activity releasing calcium and phosphate from the bones
Increases calcium reabsorption in the kidneys and acts as a phosphaturic agent
Increases hydroxylation of 1-hydroxycholecalciferol in the kidney to 1,25-dihydroxycholecalciferol which acts to increase calcium uptake from the intestines
Primary hyperparathyroidism clinical features
Symptoms- signs relating to hypercalcaemia
Bone pain, fractures and osteopenia/osteoporosis
HTN
Signs of hypercalcaemia
Weak, tired, depressed, thirsty Dehydrated but polyuric Renal stones Abdominal pain Pancreatitis Ulcers Psychosis
Tests for primary hyperparathyroidism
Calcium (increased) PTH (increased) Phosphate (decreased) ALP (increased) Pepper pot skull on XR DEXA for osteoporosis
Secondary hyperparathyroidism
Low calcium
Appropriately raised PTH
Aetiology of secondary hyperparathyroidism
Decreased vitamin D intake
Chronic renal failure
Tertiary hyperparathyroidism
Increased calcium
Inappropriately increased PTH
Prolonged secondary hyperparathyroidism the glands act autonomously having undergone hyperplastic change
Signs of hypocalcaemia
Tetany- twitching, cramping, spasm Depression Cataracts QT prolongation Trousseau's sign- BP cuff inflated Chvostek's sign- tapping of parotid gland results in facial nerve twitching Perioral paraesthesia
Causes of hypocalcaemia
Vit D deficiency Renal disease Hypomagnesaemia Hypoparathyroidism End organ resistance to PTH or Vit D
von-Hippel Lindau syndrome
Mutation of a tumour suppressor gene resulting in renal cysts and cancer, retinal and cerebellar haemangioblastoma and phaeochromocytoma
Peutz-Jegher’s syndrome
Mutation of a tumour suppressor gene resulting in mucocutaneous dark freckles on lips, oral mucosa, palms and soles and multiple GI polyps- raising GI cancer risk by 15 fold
Multiple Endocrine Neoplasm 1
Parathyroid hyperplasia
Pancreas endocrine tumours- gastrinoma or insulinoma
Pituitary prolactinoma or GH secreting tumour (acromegaly)
MEN-2a
Thyroid medullary carcinoma- 100%
Phaeochromocytoma
Parathyroid hyperplasia
MEN-2b
Similar to MEN-2a but with mucosal neuromas and marfanoid appearance without hyperparathyroidism
Side effects of steroids
GI- peptic ulcer, acute pancreatitis
Endocrine- Cushing’s syndrome- intrascapular fat pad, moon-face, thin limbs, central obesity, impaired glucose tolerance leading to T2DM, increased appetite and weight gain
Immunosuppression
Growth suppression in children
Neutrophilia
MSK- proximal muscle myopathy, osteoporosis, avascular necrosis of the femoral head
Easy bruising, thinning of the skin
Ophthalmic- glaucoma, cataracts
Psychiatric- insomnia, psychosis, mania, depression
Fluid retention
Hypertension from the mineralocorticoid activity
Adrenal cortex areas and steroids produced
Zona glomerulosa- mineralocorticoids
Zona fasciculata- glucocorticoids
Zona reticularis- androgens
HPA axis
CRH (hypothalamus)–>ACTH (anterior pituitary)–> cortisol and androgens (cortex)
ACTH dependent causes of Cushing’s syndrome
Cushing’s disease- bilateral adrenal hyperplasia from an ACTH secreting pituitary adenoma
Ectopic ACTH production- small cell lung carcinoma and carcinoid tumours
ACTH independent causes of Cushing’s sydrome
Iatrogenic- steroids
Adrenal cancer
Adrenal nodular hyperplasia
Investigating suspected Cushing’s syndrome
1st line tests
Overnight dexamethasone suppression test- 1mg at midnight, serum cortisol at 8am- normally should suppress but not in Cushing’s
24 hour free cortisol
2nd line tests
48 hour dexamethasone suppression test- give for 2 days and measure cortisol at 0 and 48hrs- failure to suppress cortisol in Cushing’s
Localising
Plasma ACTH- if undetectable then ACTH independent- adrenal tumour likely
Treatment for Cushing’s syndrome
Depends on the cause
Stop medications
Removal of pituitary adenoma if Cushing’s disease
Adrenalectomy
If ectopic ACTH then locate and surgery if not spread
What is Addison’s disease?
Primary adrenal insufficiency
Aetiology of Addison’s disease
Autoimmune TB Adrenal metastases Lymphoma Opportunistic infections Adrenal haemorrhage Secondary from long term steroid use
Symptoms of Addison’s disease
Lean, tanned, tearful and tired Weakness Anorexia Faints Myalgias and arthralgias Depression and psychosis Nausea and vomiting, abdo pain, diarrhoea or constipation
Investigations for Addison’s disease
Low mineralocorticoids leading to low sodium and raised potassium
Low glucose due to low glucocorticoid
Raised calcium
Short ACTH test- synacthen test- plasma cortisol before and after- expecting low cortisol (excluded above 550)
9AM ACTH inappropriately high
21 hydroxylase adrenal autoantibodies in 80%
Plasma renin and aldosterone to assess mineralocorticoid status
Treatment for Addison’s disease
Replace steroids- hydrocortisone and mineralocorticoid- fludrocortisone
Primary hyperaldosteronism
Excess production of aldosterone resulting in increased sodium and water retention and decreased renin release
Hypokalaemia and alkalosis
Signs of hypokalaemia
Weakness, cramps, worsening DM control or polyuria
Palpitations
Psychological symptoms
Aetiology of primary hyperaldosteronism
2/3 are Conn’s syndrome- aldosterone producing adenoma
1/3 due to bilateral adrenal hyperplasia
Secondary hyperaldosteronism
Due to increased renin from decreased renal perfusion
Renal artery stenosis, HTN, CCF
Tests for hyperaldosteronism
U&Es
Renin and aldosterone ratio
Treatment for hyperaldosteronism
Conn’s- laparoscopic adrenalectomy
Adrenal hyperplasia- medical management with an MRA
Classic symptoms of phaeochromocytoma
Sweating, episodic headache, tachycardia
Palpitations, anxiety, pallor
Investigating phaeochromocytoma
24 urinary metanephrines
Treatment of phaeochromocytoma
Alpha blockade (phenoxybenzamine) then beta blockade (to avoid unopposed alpha adrenergic stimulation) Surgery
When to think of Conn’s with HTN
Hypokalaemia
Refractory (more than 3 drugs)
Early onset HTN <40, especially women
What is virilism
The appearance of male secondary sexual characteristics in women
Polycystic ovarian syndrome clinical features
Bilateral polycystic ovaries (on ultrasound) Oligo or amenorrhoea Infertility Hirsutism Obesity Acne
Management of PCOS
Healthy eating, optimize weight, shaving, laser photoepilation, wax, electrolysis
Oestrogens
Metformin and spironolactone
Clomifene for infertility
The big three: organic causes of erectile dysfunction
Diabetes
Smoking
Alcohol
Workup for erectile dysfunction
Full sexual and psychological history
U&Es, LFT, glucose, TFT, LH, FSH, lipids, testosterone, prolactin and Doppler- penile arterial inflow
Side effects of sildenafil
Headache
Flushing
Dyspepsia
Transient blue-green tingeing of vision
Features of local pressure from a pituitary adenoma
Headache
Visual field defects- bilateral temporal hemianopia- compression of the optic chiasm
palsy of cranial nerves III,IV,VI- pressure or invasion of the cavernous sinus
Diabetes insipidus
Disturbance of sleep and appetite
What is pituitary apoplexy?
Rapid pituitary enlargement from bleeding into a tumour
Mass effects, cardiovascular collapse due to hypopituitarism
Sudden headache, meningism, decreasing GCS, visual defect
Signs of acromegaly
Increased growth of hands, jaw and feet Coarsening facial features Macroglossia Skin darkening Acanthosis nigricans Obstructive sleep apnoea Goitre Proximal weakness and arthropathy Carpal tunnel signs Signs from pituitary mass
Complications of acromegaly
Impaired glucose tolerance
Vascular- cardiomyopathy, increased BP, LV hypertrophy,
Increased risk of colon cancer
Why is random GH not an accurate test for acromegaly?
Secreted in a pulsatile fashion
Samples should be collected every 30 minutes
What is diabetes insipidus?
Passage of large volumes of dilute urine due to impaired water resorption by the kidneys because of reduced ADH secretion from the posterior pituitary (cranial) or impaired response to ADH in the kidney (nephrogenic)
Causes of cranial diabetes insipidus
Tumour- craniopharyngioma, mets, pituitary Trauma Infiltration- sarcoidosis Vascular- haemorrhage Infection- meningoencephalitis
Causes of nephrogenic diabetes insipidus
Inherited Metabolic- low potassium, high calcium Drugs- lithium CKD Post-obstructive uropathy
How to calculate serum osmolality
(2xNa) + glucose + urea
How to exclude DI with urine and serum osmolality
If the ratio of urine:serum osmolality is greater than 2:1
Diagnosis of diabetes insipidus
Water deprivation test for 8 hours
Testing the kidneys ability to concentrate urine when dehydrated
First line antihypertensive in a black T2DM of 59 years old
ARB- eg. losartan
