Endocrine Flashcards
What is the cause of excessive sweating and oily skin in acromegaly?
caused by sweat gland hypertrophy
4 Complications of acromegaly
- HTN
- DM
- CARDIOMYOPATHY
- COLORECTAL CANCER
What is the confirmatory test of acromegaly if IGF-1 LEVEL is raised ?
Oral glucose tolerance test
In Oral glucose tolerance test
in normal patients GH is suppressed to < …….. mu/L with hyperglycaemia
< 2
Acromegaly: management
Trans-sphenoidal surgery is the first-line treatment for acromegalyin the majority of patients.
If a pituitary tumour is inoperable or surgery unsuccessful then medication may be indicated:
- somatostatin analogue : octreotide
- pegvisomant
- dopamine agonists : bromocriptine
External irradiation is sometimes used for older patients or following failed surgical/medical treatment
somatostatin analogue directly inhibits ……
the release of growth hormone
GH receptor antagonist ( pegvisomant ) - prevents ….
dimerization of the GH receptor
10 Acute phase proteins
- CRP
- procalcitonin
- ferritin
- fibrinogen
- alpha-1 antitrypsin
- caeruloplasmin
- serum amyloid A
- serum amyloid P component**
- haptoglobin
- complement
During the acute phase response the liver decreases the production of other proteins ( negative acute phase proteins)
(5)
albumin
transthyretin (formerly known as prealbumin)
transferrin
retinol binding protein
cortisol binding protein
causes of hypoadrenalism
Primary causes
1. tuberculosis
2. metastases(e.g. bronchial carcinoma)
3. meningococcal septicaemia (Waterhouse-Friderichsen syndrome)
4. HIV
5. antiphospholipid syndrome
Secondary causes
- pituitary disorders (e.g. tumours, irradiation, infiltration)
Exogenous glucocorticoid therapy
Management of addisonian crisis
- hydrocortisone 100 mg im or iv continue 6 hourly until the patient is stable.
- oral replacement may begin after 24 hours and be reduced to maintenance over 3-4 days
Causes of raised alkaline phosphatase (ALP)
liver: cholestasis, hepatitis, fatty liver, neoplasia
Paget’s
osteomalacia
bone metastases
hyperparathyroidism
renal failure
physiological:pregnancy, growing children, healing fractures
2 Causes of Raised ALP and raised calcium
Bone metastases
Hyperparathyroidism
Children are screened for Congenital hypothyroidism at …. days using …….. test
Children are screened at 5-7 days using the heel prick test
In Toxic multinodular goitre
The treatment of choice is …..
radioiodine therapy.
painful goitre and raised ESR
Subacute thyroiditis (de Quervain’s)
Management of Thyroid eye disease
smoking cessation
topical lubricants may be needed to help prevent corneal inflammation caused by exposure
steroids
radiotherapy
surgery
4 phases of Subacute thyroiditis
phase 1 (lasts 3-6 weeks): hyperthyroidism,painful goitre,raised ESR
phase 2 (1-3 weeks): euthyroid
phase 3 (weeks - months): hypothyroidism
phase 4: thyroid structure and function goes back to normal
thyroid scintigraphy:globally reduced uptake of iodine-131
In which condition?
Subacute thyroiditis
Riedel’s thyroiditis is associated with ……..
retroperitoneal fibrosis.
SGLT-2 inhibitors reversibly inhibit ……..
sodium-glucose co-transporter 2 (SGLT-2) in the renal proximal convoluted tubule to reduce glucose reabsorption and increase urinary glucose excretion
Side effects of SGLT2
urinary and genital infection (secondary to glycosuria).Fournier’s gangrene has also been reported
normoglycaemic ketoacidosis
increased risk of lower-limb amputation: feet should be closely monitored
women with established hypothyroidism who become pregnant should have their dose increased ‘by
At least 25 - 50 mcg levothyroxine
Mechanism of action of Carbimazole
blocks thyroid peroxidase from coupling and iodinating the tyrosine residues on thyroglobulin → reducing thyroid hormone production
Adverse effects of carbimazole
agranulocytosis
crosses the placenta, but may be used in low doses during pregnancy
Autoantibodies of Graves’ disease
TSH receptor stimulating antibodies(90%)
anti-thyroid peroxidase antibodies (75 %)
Thyroid scintigraphy
diffuse, homogenous, increased uptakeof radioactive iodine
In which condition?
Graves’ disease
Radioiodine treatment is contraindicated in
- pregnancy (should be avoided for 4-6 months following treatment)
- age < 16 years. T
- Thyroid eye disease is a relative contraindication, as it may worsen the condition
Hashimoto’s thyroiditis is associated with the development of……lymphoma
MALT lymphoma
Management of papillary and follicular cancer
total thyroidectomy
followed by radioiodine (I-131) to kill residual cells
yearly thyroglobulin levels to detect early recurrent disease
What is the most commonly can cause ectopic ACTH production
small cell lung cancer
ACTH independent causes of Cushing’s syndrome
iatrogenic:steroids
adrenal adenoma (5-10%)
adrenal carcinoma (rare)
Carney complex: syndrome including cardiac myxoma
micronodular adrenal dysplasia (very rare)
What is Pseudo-Cushing’s?
alcohol excessor severe depression
causes false positive dexamethasone suppression test or 24 hr urinary free cortisol
insulin stress test may be used to differentiate
Tests to confirm Cushing’s syndrome
L
- overnight (low-dose) dexamethasone suppression test
this is the most sensitive test and is now used first-line to test for Cushing’s syndrome
- 24 hr urinary free cortisol
two measurements are required
- bedtime salivary cortisol
two measurements are required
Causes of Decreased excretion of Uric acid
drugs: low-dose aspirin, diuretics, pyrazinamide
pre-eclampsia
alcohol
renal failure
lead
Increased synthesis of Uric acid
Lesch-Nyhan disease
myeloproliferative disorders
diet rich in purines
exercise
psoriasis
cytotoxics
4 Causes of Hypokalaemia with hypertension
Cushing’s syndrome
Conn’s syndrome (primary hyperaldosteronism)
Liddle’s syndrome
11-beta hydroxylase deficiency*
- 2CL11
5 causes of hypokalaemia without hypertension
- Diuretics
- Bartter’s syndrome
- Gitelman syndrome
- GI loss ( diarrhoea, vomiting)
- RTA ( type 1 & 2)
Bartter’s syndrome is autosomal ………
autosomal recessive
Bartter’s syndrome cause severe hypokalaemia due to defective ………..
chloride absorption at theNa+K+2Cl- cotransporter (NKCC2) in the ascending loop of Henle
Features of Bartter’s syndrome
- usually presents in childhood, e.g. Failure to thrive
- polyuria, polydipsia
- hypokalaemia
- normotension
- weakness
Autoimmune polyendocrinopathy syndrome type 1
(2 out of 3 needed)
- chronic mucocutaneous candidiasis (typically first feature as young child)
- Addison’s disease
- primary hypoparathyroidism
- Vitiligo can occur
Autoimmune polyendocrinopathy syndrome type 2
Addison’s disease plus either:
- T1DM
- autoimmune thyroid disease
- Vitiligo can occur
Management of Diabetic neuropathy
first-line treatment:amitriptyline, duloxetine, gabapentin or pregabalin
if the first-line drug treatment does not work try one of the other 3 drugs
tramadol may be used as ‘rescue therapy’ for exacerbations of neuropathic pain
topical capsaicin may be used for localised neuropathic pain (e.g. post-herpetic neuralgia)
pain management clinicsmay be useful in patients with resistant problems
Management of Gastroparesis
metoclopramide or
domperidone or
erythromycin
3 Causes of higher than expected levels of HbA1c
Vitamin B 12 / folic acid deficiency
IDA
Splenectomy
glycaemic index (GI) describes ….
capacity of a food to raise blood glucose compared with glucose in normal glucose-tolerant individuals
Mechanism of action of Metformin
- Increases insulin sensitivity
- Decreases hepatic gluconeogenesis
Metformin is contraindicated if GFR
< 30
Sulfonylureas Stimulate
pancreatic beta cells to secrete insulin
Mechanism of action of Thiazolidinediones
Activate PPAR-gamma receptor in adipocytes to promote adipogenesis and fatty acid uptake
DPP-4 inhibitors (-gliptins) Increases
incretin levels which inhibit glucagon secretion
SGLT-2 inhibitors (-gliflozins) Inhibits
reabsorption of glucose in the kidney
Mechanism of action of GLP-1 agonists(-tides)
Incretin mimetic which inhibits glucagon secretion
adverse effects of sulfonylureas
- Hypoglycemia
- Weight gain
- Hypo Na
- bone marrow suppression
- hepatotoxicity(typically cholestatic)
- peripheral neuropathy
Sulfonylureas vs breastfeeding
should be avoided
Sulfonylureas
On a molecular level they bind ……..?……..on the cell membrane of pancreatic beta cells.
to an ATP-dependent K+(KATP) channel
5 Side effects of Thiazolidinediones
- Weight gain
- Liver Impairment
- Fluid retention
- Increase risk of fractures
- Bladder cancer
prediabetes
- FBG
- HbA1C
- 6.1-6.9 mmol/l
- 42-47 mmol/mol (6.0-6.4%)
Phaeochromocytoma may be associated with
MEN type II,
neurofibromatosis and
von Hippel-Lindau syndrome
Tests of Phaeochromocytoma
- 24 hr urinary collection of metanephrines(sensitivity 97%*)
- 24 hr urinary collection of catecholamines (sensitivity 86%)
Management of Phaeochromocytoma
Surgery is the definitive management. The patient must first however be stabilized with medical management:
alpha-blocker (e.g. phenoxybenzamine), given before a
beta-blocker (e.g. propranolol)
the most common cause of Primary hyperaldosteronism
bilateral idiopathic adrenal hyperplasia: the cause of around 60-70% of cases
Investigations of Primary hyperaldosteronism
- plasma aldosterone/renin ratio is the first-line investigationin suspected primary hyperaldosteronism
- should show high aldosterone levels alongside low renin levels
- following this a high-resolution CT abdomen and adrenal vein sampling is used to differentiate between unilateral and bilateral sources of aldosterone excess
- if the CT is normal adrenal venous sampling (AVS)can be used to distinguish between unilateral adenoma and bilateral hyperplasia
Management of Primary hyperaldosteronism
adrenal adenoma: surgery (laparoscopic adrenalectomy)
bilateral adrenocortical hyperplasia:aldosterone antagonist e.g. spironolactone
Drugs causing SIADH
sulfonylureas*
SSRIs, tricyclics
carbamazepine
vincristine
cyclophosphamide
Causes of SIADH
- Malignancy
small cell lung cancer
also: pancreas, prostate
- Neurological
Stroke
SAH
SUBDURAL HEMORRHAGE - Infections
TB
Pneumonia - Other causes
positive end-expiratory pressure (PEEP)
porphyrias
Investigations of SIADH
Urine osmolality: Urine osmolality is inappropriately high (>100 mOsm/kg) in relation to serum osmolality, as the kidneys should normally dilute urine in the setting of low serum osmolality.
Urine sodium concentration: >40 mmol/L)
Management of SIADH
correction must be done slowly to avoid precipitating central pontine myelinolysis
fluid restriction
demeclocycline: reduces the responsiveness of the collecting tubule cells to ADH
ADH (vasopressin) receptor antagonists have been developed
3 Contraindications of insulin stress test
- Epilepsy
- IHD
- ADRENAL INSUFFICIENCY
Risk factors for gestational diabetes
BMI of > 30 kg/m²
previous macrosomic baby weighing 4.5 kg or above
previous gestational diabetes
first-degree relative with diabetes
family origin with a high prevalence of diabetes (South Asian, black Caribbean and Middle Eastern)
Screening for gestational diabetes with
OGTTis the test of choice
Pregnant women with any of the other risk factors should be offered an OGTT at…..?
at 24-28 weeks
Diagnostic thresholds for gestational diabetes
FBG >= 5.6 MMOL / L
2Hr GLUCOSE >= 7.8 MMOL / L
Management of gestational diabetes
- if the fasting plasma glucose level is< 7 mmol/l a trial of diet and exercise should be offered
if glucose targets are not met within 1-2 weeks of altering diet/exercise metformin should be started
if glucose targets are still not met insulin should be added to diet/exercise/metformin
gestational diabetes is treated short-acting, not long-acting, insulin
- if at the time of diagnosis the fasting glucose level is >= 7 mmol/l insulin should be started
- if the plasma glucose level is between 6-6.9 mmol/l, and there is evidence of complications such as macrosomia or hydramnios, insulin should be offered
Targets for self monitoring of pregnant women (pre-existing and gestational diabetes)
Fasting …….?
1 hr after meal …….?
2 hr after meal …….?
Fasting 5.3
1 hr after meal 7.8
2 hr after meal 6.4
Meglitinides increase
pancreatic insulin secretion like sulfonylureas theybind to an ATP-dependent K+(KATP) channel on the cell membrane of pancreatic beta cells
MODY associated with HNF1A often respond well to treatment with ……?
low-dose sulfonylureas
The most common types of MODY
MODY2 (GCK mutation)
Causes of hypoglycemia
insulinoma - increased ratio of proinsulin to insulin
self-administration of insulin/sulphonylureas
liver failure
Addison’s disease
alcohol
nesidioblastosis - beta cell hyperplasia
Physiological response to hypoglycaemia
hormonal response: the first response of the body is decreased insulin secretion. This is followed byincreased glucagon secretion. Growth hormone and cortisol are also released but later
sympathoadrenal response: increased catecholamine-mediated (adrenergic) and acetylcholine-mediated (cholinergic) neurotransmission in the peripheral autonomic nervous system and in the central nervous system
Very high glucocorticoid activity, minimal mineralocorticoid activity
Which preparation?
Dexamethasone
Betmethasone
Glucocorticoid activity, high mineralocorticoid activity,
Which preparation?
Hydrocortisone
Predominant glucocorticoid activity, low mineralocorticoid activityVery high glucocorticoid activity, minimal mineralocorticoid
Which preparation?
Prednisolone
Minimal glucocorticoid activity, very high mineralocorticoid activity,
Which preparation?
Fludrocortisone
theBNF suggests gradual withdrawal of systemic corticosteroids if patients have:
(3)
- received more than 40mg prednisolone daily for more than one week
- received more than 3 weeks of treatment
- recently received repeated courses
Mineralocorticoid side-effects
fluid retention
hypertension
ophthalmic Glucocorticoid side-effects
glaucoma
cataracts
psychiatric Glucocorticoid side-effects
insomnia
mania
depression
psychosis
Causes of Hypokalaemia with alkalosis
vomiting
thiazideand loop diuretics
Cushing’s syndrome
Conn’s syndrome (primary hyperaldosteronism)
6 Causes of Hypophosphataemia
alcohol excess
acute liver failure
diabetic ketoacidosis
refeeding syndrome
primary hyperparathyroidism
osteomalacia
Liddle’s syndrome is
HTN
HYPOKALAEMIC ALKALOSIS
Treatment of Liddle’s syndrome
Treatment is with either amiloride or triamterene
Causes of primary hyperparathyroidism
85%: solitary adenoma
10%: hyperplasia
4%: multiple adenoma
1%: carcinoma
Pendred’s syndrome
bilateral sensorineural deafness, with mild hypothyroidism and a goitre
Treatment of Pendred’s syndrome
Treatment is with thyroid hormone replacement and cochlear implants.
Pseudohypoparathyroidism
Associated with
Labs ?
associated with low IQ, short stature, shortened 4th and 5th metacarpals
low calcium, high phosphate, high PTH
diagnosis is made by measuring urinary cAMP and phosphate levels following an infusion of PTH
What’s Pseudopseudohypoparathyroidism?
similar phenotype to pseudohypoparathyroidism but normal biochemistry
Pseudohypoparathyroidism is caused by
target cell insensitivity to parathyroid hormone (PTH) due to a mutation in a G-protein.
Investigations of Pseudohypoparathyroidism
↑ PTH
↓ calcium
↑ phosphate
infusion of PTH followed by measurement of urinary phosphate and cAMP measurement - this can help differentiate between type I (neither phosphate or cAMP levels rise) and II (cAMP rises but phosphate levels do not change)
Type 1 vs type 2 of pseudohypoparathyroidism
Type 1 »_space;> complete receptor defect
type 2»> the cell receptor is intact
Drug causes of raised prolactin
metoclopramide, domperidone
phenothiazines
haloperidol
very rare: SSRIs, opioids
Causes of raised prolactin
prolactinoma
pregnancy
oestrogens
physiological: stress, exercise, sleep
acromegaly: 1/3 of patients
polycystic ovarian syndrome
primary hypothyroidism (due to thyrotrophin releasing hormone (TRH) stimulating prolactin release)
Drugs
Pituitary adenomas can be classified according to size
microadenoma is <1cm
macroadenoma is ≥1cm)
Orlistat is a…………………… inhibitor
pancreatic lipase inhibitor
criteria for use Liraglutide in obesity
- BMI >= 35
- Pre diabetes
Galactosaemia is a rare autosomal …1…….. condition caused by …..2…..
- autosomal recessive
- the absence of galactose-1-phosphate uridyl transferase
Features of Galactosaemia
jaundice
failure to thrive
hepatomegaly
cataracts
hypoglycaemia after exposure to galactose
Fanconi syndrome
Causes of gynaecomastia
physiological: normal in puberty
syndromes with androgen deficiency: Kallman’s, Klinefelter’s
testicular failure: e.g. mumps
liver disease
testicular cancer e.g. seminoma secreting hCG
ectopic tumour secretion
hyperthyroidism
haemodialysis
drugs:
Drug causes of gynaecomastia
spironolactone (most common drug cause)
cimetidine
digoxin
cannabis
finasteride
GnRH agonists e.g.goserelin, buserelin
oestrogens, anabolic steroids
Very rare drug causes of gynaecomastia
tricyclics
isoniazid
calcium channel blockers
heroin
busulfan
methyldopa
Causes of predominantly hypertriglyceridaemia
diabetes mellitus (types 1 and 2)
obesity
alcohol
chronic renal failure
drugs: thiazides, non-selective beta-blockers, unopposed oestrogen
liver disease
Causes of predominantly hypercholesterolaemia
nephrotic syndrome
cholestasis
hypothyroidism
Water deprivation test
Inpsychogenic polydipsia
- Sarting Plasma Osmolality
- Final urine osmolality
- Urine osmolality post DDAVP
- Low
- > 400
- > 400
Water deprivation test
Incranial DI
- Sarting Plasma Osmolality
- Final urine osmolality
- Urine osmolality post DDAVP
- High
- <300
- > 600
Water deprivation test
Innephrogenic DI
- Sarting Plasma Osmolality
- Final urine osmolality
- Urine osmolality post DDAVP
- High
- < 300
- < 300
Water deprivation test
Innormal
- Sarting Plasma Osmolality
- Final urine osmolality
- Urine osmolality post DDAVP
- Normal
- > 600
- > 600
Risk factors of Urinary incontinence
advancing age
previous pregnancy and childbirth
high body mass index
hysterectomy
family history
Immediate release oxybutynin should, however, beavoided in …..?
frail older women’
theRotterdam criteriastate that a diagnosis of PCOS can be made if 2 of the following 3 are present:
- infrequent or no ovulation (usually manifested as infrequent or no menstruation)
- clinical and/or biochemical signs of hyperandrogenism (such as hirsutism, acne, or elevated levels of total or free testosterone)
- polycystic ovaries on ultrasound scan (defined as the presence of ≥ 12 follicles (measuring 2-9 mm in diameter) in one or both ovaries and/or increased ovarian volume > 10 cm³)
Treatment of Hirsutism and acne (PCOS)
- third generation OCP which has fewer androgenic effects or co-cyprindiol which has an anti-androgen action.
- if doesn’t respond then topical eflornithine may be tried
- spironolactone, flutamide and finasteride may be used under specialist supervision
Treatment of infertility in PCOS
metformin is also used, either combined with clomifene or alone, particularly in patients who are obese
gonadotrophins
Treatment of Premature ovarian insufficiency
hormone replacement therapy (HRT) or a combined oral contraceptive pill should be offered to women until the age of the average menopause (51 years)
it should be noted that HRT does not provide contraception, in case spontaneous ovarian activity resumes
Risk factors of ovarian cancer
family history: mutations of theBRCA1or theBRCA2 gene
many ovulations*:early menarche,late menopause,
Investigations of ovarian cancer
- CA 125 if >= 35 IU/ML THEN ultrasound of abdomen and pelvis should be ordered
Neuroblastoma arises from …….
neural crest tissue of the adrenal medulla (the most common site) and sympathetic nervous system.
MEN tpye 1
3 Ps
- Pituitary tumour: prolactinoma
- Primary hyperparathyroidism
- Pancreatic tumour: gastrinoma , insulinoma
MEN type 2a
2Ps
- Primary hyperparathyroidism
- Phaeochromocytoma
- Medullary thyroid cancer
MEN TYPE 2b
1P
- Phaeochromocytoma
- Medullary thyroid cancer
- Marfanoid body habitus
The most common presentation of MEN1
Hypercalcaemia
RET oncogene can be found in
MEN type 2a & 2b
For a diagnosis of metabolic syndrome at least 3 of the following should be identified:
- FBG > 5.6 mmol / L
- BP > 130 / 85 or active treatment of HTN
- HDL < 1.03 in males or < 1.29 in females
- Waist circumference : men > 102 cm , women > 88 cm
Potential complications of Hormone replacement therapy
- increased risk of breast cancer
- increased risk of endometrial cancer
- increased risk of venous thromboembolism
- increased risk of stroke
- increased risk of IHD
Fibrates work throughactivating ………..resulting in an increase in ………….. reducing triglyceride levels.
activating PPAR alpha receptors resulting in an increase in LPL activity reducing triglyceride levels.
Fibrates side effects
gastrointestinal side-effects are common
increased risk of thromboembolism
Ezetimibe is a lipid-lowering drug which inhibits ………….., decreasing cholesterol absorption in …………
inhibits cholesterol receptors on enterocytes,
decreasing cholesterol absorption in the small intestine.
for treating primary hypercholesterolaemia in adults in whom initial statin therapy is contraindicated or who cannot tolerate statin therapy, recommended to start …..
Ezetimibe
one parent is affected by familial hypercholesterolaemia, arrange testing in children by age ….?
by age 10
if both parents are affected by familial hypercholesterolaemia, arrange testing in children by age …..?
by age 5
statins should be discontinued in women ……. months before conception due to the risk of congenital defects
3 months
insulinoma is a neuroendocrine tumour deriving mainly from ………?
from pancreatic Islets of Langerhans cells
Diagnosis of insulinoma
supervised, prolonged fasting (up to 72 hours)
CT pancreas
Management of insulinoma
surgery
diazoxide and somatostatin if patients are not candidates for surgery
Klinefelter’s syndrome is associated withkaryotype ……..
karyotype 47, XXY.
Diagnosis of Klinefelter’s syndrome by
By karyotype ( chromosomal analysis )
Features of which condition?
often taller than average
lack of secondary sexual characteristics
small, firm testes
infertile
gynaecomastia- increased incidence of breast cancer
elevated gonadotrophin levels but low testosterone
Klinefelter’s syndrome
Managment of Klinefelter’s syndrome
testosterone supplementation
gonadotrophin supplementation may result in sperm production if fertility is desired later in life
4 Risk factors of Endometrial cancer
- hereditary non-polyposis colorectal carcinoma
- Metabolic syndrome
- tamoxifen
- excess oestrogen ( early menarche, late menopause)
3 Protective factors of endometrial cancer
multiparity
combined oral contraceptive pill
smoking(the reasons for this are unclear)
What is the most important factor in the development of cervical cancer
Human papillomavirus (HPV), particularly serotypes 16,18 & 33
Cervical cancer may be divided into :
squamous cell cancer (80%)
adenocarcinoma (20%)
7 Risk factors of cervical cancer
- Smoking
- HIV
- HPV
- early first intercourse,many sexual partners
- High parity
- Combined OCP
- Lower socio-economic status
Causes of Congenital adrenal hyperplasia
21-hydroxylase deficiency (90%)
11-beta hydroxylase deficiency (5%)
17-hydroxylase deficiency (very rare
- 11, 17 , 21
Androgen insensitivity syndrome is condition due to end-organ resistance to testosterone causing genotypically male children (…..XY) to have a female phenotype.
(46XY)
Management of androgen insensitivity syndrome
counselling - raise the child as female
bilateral orchidectomy (increased risk of testicular cancer due to undescended testes)
oestrogen therapy
Metabolic syndrome associated with
- High uric acid
- NAFLD
- PCOS
Serum osmolality in HHS
> 320 mosmol/kg
