Endocrine II Flashcards
What are the two types of DI?
Cranial - low ADH
Nephrogenic - not responsive to ADH
Which two drugs can cause DI?
Lithium
Demeclocycline
How is DI diagnosed?
Fluid depravation for 8h, then ADH
Step 1 - fluid depravation
- If urine osmolality >600 then stop
- If urine osmolality <600 then continue to stage 2
Step 2 - give desmopressin IM
- Cranial DI: urine osmolality increases to >600 after desmopressin
- Nephrogenic DI: no increase in urine osmolality after desmopressin
Treatment of nephrogenic DI?
NSAIDs
Thiazides
Treatment of hirsutism?
Cyproterone
Definitive test for acromegaly?
Oral glucose tolerance test (suppression test)
Rising levels of glucose inhibit GH secretion
In healthy patient, in OGTT, GH levels should be undetectable
In acromegaly, there is failure to suppress GH secretion
Patient >60 with bone pain, hypercalcaemia, increased ALP = ?
Multiple myeloma
Osteolytic lesions seen on x-ray
Really long arms + legs + gynaecomastia = ?
Klinefelter’s syndrome
List three clinical features of Kartagener’s syndrome
Dextrocardia
Abnormal frontal sinus
Primary ciliary dyskinesia
Decreased anti-malarian hormone + increased FSH = ?
Reduced ovarian reserve
In hypopituitarism, which hormones area affected in which order?
GH FSH + LH PRL TSH ACTH
Describe the treatment for hypopituitarism
- Hydrocortisone - before any other hormone
- Thyroxine if hypothyroid
- Men - testosterone replacement
- Women (premenopausal) - oestrogen patches or contraceptive pill
- Gonadotrophin therapy is needed to induce fertility in both men and women
- GH - refer to endocrinologist for insulin tolerance testing
Treatment of chlamydia?
Azithromycin
What is Sheehan’s syndrome?
Post partum hypopituitarism caused by ischaemic necrosis due to blood loss and hypocolaemic shock during and after childbirth
WHAT DO STEROIDS DO TO BLOOD GLUCOSE LEVELS
STEROIDS INCREASE BLOOD GLUCOSE LEVELS
List the four main functions of cortisol
- Maintain normal plasma glucose levels
- Under stress it allows the body to have a fuel source
- Increased responsiveness of adrenoreceptors to adrenaline - helps with circulation to prevent patient going into shock
- Anti-inflammatory roles at high levels
What effect does cortisol have on metabolism?
Increases the amount of raw material that the body can use as energy in times of stress
- Increases lipolysis
- Decreases glucose uptake into tissues
- Increases gluconeogenesis
- Increases proteolysis
What does uncontrolled secretion of cortisol do to blood glucose?
Dramatically increases blood glucose
If cortisol increases blood glucose, what symptoms will this give the patient?
Polyuria
Polydipsia
What is the classic triad of symptoms of excess adrenaline?
Hypertension
Sweating
Headaches
What is the stimulus for erythropoietin secretion?
Hypoxia - causes stem cells in the bone marrow to produce RBCs to increase the oxygen carrying capacity of the blood
What is calcidiol?
A prehormone produced in the liver, originating in the skin
In the kidneys is is converted to calcitriol
This is stimulated by PTH
What are the two roles of angiotensin II?
Directly vasoconstricts
Indirectly elevates BP by aldosterone
What should you think of cortisol as?
A stress hormone
What are the three main clinical uses of corticosteroids?
- Suppress inflammation e.g. asthma
- Suppress immune system e.g. autoimmune conditions - Crohn’s
- Replace treatment - for people who don’t produce enough
What are the end product deficiencies in each of these enzymatic deficiencies?
- 21aOH
- 11bOH
- 17aOH
21aOH - problem with glucocorticoid and mineralocorticoid -> increased androgen
11bOH - problem with glucocorticoid and mineralocorticoid -> increased androgen
17aOH - problem with glucocorticoid and androgen -> normal aldosterone
What are the clinical features of 11bOH deficiency?
Females virilised
Salt wasting rare
What are the clinical features of 17aOH deficiency?
Males virilised
Females fail to achieve puberty
Salt wasting not observed
What is significant about hypovolaemia in hyponutraemia?
This implies that there is a very big sodium deficit
Must give the patient the sodium which they lack
What does oedema tell you?
Water is in the wrong place
You are likely to have too much sodium, in the wrong place
Which genes are associated with
- Carney complex
- McCune-Albright
- Von Hippel-Lindau disease
- Nerofibromatosis type I
Carney complex - PRKAR1A
McCune-Albright - GNAS1
Von Hippel-Lindau disease - VHL
Nerofibromatosis type I - NF1
What are glucose levels in Addison’s?
Low - CORTISOL INCREASES GLUCOSE LEVELS
List some causes of primary and secondary adrenal insuffifiency
Primary - Addisons - CAH - TB, tumor Secondary - Exogenous steroid use - Pituitary/hypothalamic tumours
Diagnosis of secondary adrenal insufficiency?
When might this be negative?
Long synacthen test
If acute this may be negative - give steroid anyway
What is biochemistry like in Addison’s?
Hyponatraemia
Hyperkalaemia
Hypercalcaemia
Hypoglycaemia
Unexplained abdominal pain + vomiting = ?
Addison’s
Which antibodies are positive in autoimmune addisons?
21-hydroxylase adrenal autoantibodies
Hypertension + hypokalaemia = ?
Primary aldosteronism
High Na
High h20 (hypertension)
Low K
= ?
Conn’s syndrome
Medical treatment of primary hyperaldosteronism?
Spironolactone - aldosterone receptor antagonist
How is diagnosis of primary hyperaldosteronism diagnosed?
First do aldosterone renin ratio - if >750 then move on to next step
Saline suppression test
Failure of aldosterone to suppress by 50% is diagnostic
How is diagnosis of congenital adrenal hyperplasia made?
Basal (or stimulated) 17-OH progesterone
Biochemistry of SIADH?
Increased ADH
Hyponatraemia
Increased urinary sodium
What is an important cause of SIADH to keep in mind?
SCLC
Treatment of SIADH?
If symptomatic then fluid restrict to 500-1000 ml in 24h
What are the three P’s of MEN1?
Parathyroid
Anterior pituitary - prolactinoma, acromegaly, Cushing’s
Enteropancreatic
Other tumours - carcinoids of thymus, lung, stomach, adrenal cortex adenomas
Genetics of MEN1?
Mutation in MEN gene on chromosome 11
Leads to loss of function of menin
Menin = nuclear tumour suppressor protein
How should you screen for MEN1?
Serum calcium
Three classic tumour types in MEN2A?
Medullary thyroid carcinoma
Adrenal medulla - phaeochromocytoma
Parathyroid hyperplasia
Three classic tumour types in MEN2B?
Medullary thyroid carcinoma
Adrenal medulla - phaeochromocytoma
Mucosal neuromas
Genetics of MEN2?
Mutation in RET proto-oncogene
How should you screen for MEN2?
Genetic testing for RET mutation
Medical treatment of phaeochromocytoma?
Alpha blockade - phenoxybenzamine
THEN
Beta blockade - atenolol
Chemotherapy - radio labelled MIBG
List the clinical features of Carney complex
ACTH independent Cushing’s
Acromegaly due to GH producing adenoma
Thyroid cancer
Spotty pigmentation of skin
Polyostotic fibrous dysplasia + Cafe-au-lait + precocious puberty + autonomous endocrine hyperfunction + scoliosis = ?
McCune-Albright syndrome
Visceral cysts and benign tumours in multiple organ systems = ?
Von Hippel Lindau disease
DI + DM + optic atrophy + deafness + neuro problems = ?
DIDMOAD or Wolfram syndrome
Obese + polydactyly + hypogonadal + visual impairment + hearing impairment + mental retardation = ?
Bardet-Biedl syndrome
Describe the process of vitamin D metabolism
Originates in skin as 7-dehydrocholesterol
UV light acts on this to produce cholecalciferol (vitamin D3)
In the liver this is converted to 25-hydroxyvitamin D3 (calcidiol)
In the kidneys this is converted by 1aOH to 1,25-dxydroxyvitamin D3 (calcitriol)
What is calcitriol and what are its functions?
Active form of vitamin D - a steroid hormone
Kidneys - increases absorption of Ca2+ and increases absorption of PO43-
Increases bone resorption to increase serum calcium
When is calcitonin secreted?
What is it’s function
In extremes of hypercalcaemia
Decrease serum calcium
Decrease serum phosphate
What does deficiency/excess calcitonin do to bone?
Has no effect
What are the two causes of hypercalcaemia to remember?
What is PTH like in each?
Primary hyperparathyroidism - high PTH
Malignancy - low PTH
What are the three types of hyperparathyroidism and what are levels of Ca and PTH like in each?
Primary - overactivity of parathyroid - increased PTH and calcium
Secondary - physiological response to low calcium - high PTH, low calcium
Tertiary - parathyroid gland becomes autonomous after many years of secondary - high PTH and high calcium
What is the most common cause of hypercalcaemia?
What is the most common cause of this condition?
Primary hyperparathyroidism
Parathyroid adenoma
What does a diagnosis of primary hyperparathyroidism require a triad of?
- Raised serum calcium
- Raised serum PTH
- Increased urine calcium excretion in the absence of diuretics
What is hypocalcuric hypercalcaemia?
AD mutation in calcium sensing receptor
Mild hypercalcaemia with reduced urine calcium excretion
PTH may be marginally elevated
Treatment of acute hypocalcaemia?
IV calcium gluconate
Biochemistry in hypoparathyroidism?
Low PTH
Low Ca
High phosphate
What is pseudohypoparathyroidism?
Genetic resistance to PTH
High PTH
Low calcium
High phosphate
Symptoms of pseudohypoparathyroidism and pseudopseudohypoparathyroism
Subcutaneous calcification
Mental retardation
Blunting of 4th metacarpal
Obesity
Treatment for Rickets?
Adcal D3
What is the preferred osteoporosis indicator?
QFracture
What should you treat osteoporosis with if bisphosphonates are giving GI side effects?
Zoledronic acid once yearly IV infusion for 3 years
If renal impairment, use Denosumab
Deafness + frontal bossing + bowing of the legs = ?
Pagets disease
Which cancer is Pagets associated with?
Osteosarcoma
Two causes of rickets + osteomalacia?
- Problem with calcium or vitamin D
2. Phosphate deficiency caused by increased renal losses
What is the function of leptin?
Tells your body how thin you are
How does orlistat work?
Inhibits lipase to block absorption of dietary fat
What are the types of gastric bypass surgery and which are restrictive/absorptive?
Banding - restrictive
Sleeve gastrectomy - restrictive
Bypass - restrictive and malabsorptive
Why are some genes activated by steroids and some suppressed?
In one gene is more numerous, then multiple GRs can bind and expression is induced
If there is only one gene expressed, then binding of the GR will block the gene and so expression is supressed
Why do some steroids cause fragile skin?
Glucocorticoids act on both GC and MR receptor
Can stop this by using something which saturates the MR receptor e.g. spironolactone cream
Treatment of osteogenesis imperfecta?
Bisphosphonates
What causes gestational diabetes?
Progesterone and hPL cause insulin resistance
Which diabetic drugs are safe in pregnancy?
Metformin
Glibenclamide
What must be checked more regularly in diabetic pregnancy?
Eye - accelerated pre-existing retinopathy
Which blood pressure drugs can be used in pregnancy?
Labetalol
Nifedipine
Methyldopa
How should you maintain good blood glucose during labour?
IV insulin
IV dextrose
What should you do post natally for gestational diabetes?
Make sure it has gone away - 6 week post natal glucose tolerance test
What should you do with hypothyroidism in pregnancy?
Increase dose of thyroxine by 25mcg as soon as pregnancy is suspected
Which condition can give similar symptoms to hyperemesis in pregnancy?
Hyperthyroidism
How should you treat hyperthyroidism in pregnancy?
Propylthiouracil 1st trimester
Carbimazole 2/3 trimester
How does treatment of DKA vary between adults and children?
Careful fluid resuscitation - risk of cerebral oedema
Insulin started one hour after IV fluid - fluids are started first
Which endocrine disorder are all babies screened for on day 5?
Congenital thyroid disease - look at TSH
Called the Guthrie test
Which beta blocker is used in thyrotoxicosis?
Propranolol (non selective)
