Y2 ENDOCRINE EVERYTHING NON THYROID OR DIABETES Flashcards
1
Q
- malaise, fatigue.
- anorexia.
- weight loss.
- craving salty food.
- dizzy spells when in warm places.
Thin patient with postural hypotension. Appears tanned with increased pigmentation in mouth and hand creases.
- low sodium + high potassium.
A
addison’s
2
Q
what is the core problem in addison’s disease?
A
adrenal insufficiency:
- reduced steroids therefore low mineralocorticoid activity.
3
Q
reduced mineralocorticoid activity means?
A
sodium won’t be retained, therefore water is also lost. K+ is retained.
- hyponatraemia and hyperkalaemia.
patient will be clinically dehydrated.
4
Q
patient’s excess pigmentation in addison’s is due to?
A
excess ACTH production by the pituitary.
ACTH is degraded to MSH.
5
Q
anterior pituitary is derived from?
A
Rathke’s pouch
6
Q
anterior pituitary secretes?
A
Trophic and non-trophic hormones:
- Trophic: TSH, ACTH, FSH, LH.
- Non-trophic: GH and prolactin.
7
Q
posterior pituitary secretes?
A
ADH and oxytocin
8
Q
posterior pituitary contains?
A
non-myelinated axons of neurosecretory neurons
9
Q
anterior pituitary acidophils?
A
GH (somatotroph) - 50% and prolactin (mammotroph) - 20%.
10
Q
anterior pituitary basophils?
A
ACTH (corticotrophs) - 20% , TSH (thyrotoph) - 5% and FSH/LH (gonadotroph) - 5%.
11
Q
what causes hyperfunction of the anterior pituitary?
A
adenoma or carcinoma
12
Q
what causes hypofunction of the anterior pituitary?
A
- surgery/radiation.
- sudden haemorrhage into gland.
- ischaemic necrosis (sheehan syndrome).
- tumours extending into sella.
- inflammatory conditions e.g. sarcoidosis.
13
Q
what results from hyperfunction of the anterior pituitary?
A
SIADH - the ectopic secretion of ADH by tumours OR due to a primary disorder of the pituitary.
14
Q
what results from hypofunction of the anterior pituitary?
A
Diabetes insipidus - a lack of ADH secretion that can lead to life-threatening dehydration.
15
Q
pituitary adenomas account for what percentage of intra-cranial tumours?
A
10%
16
Q
pituitary adenomas may be sporadic or ass. with?
A
MEN1
17
Q
large pituitary adenomas may cause?
A
- visual field defects.
- pressure atrophy of surrounding tissue.
- infarction leading to panhypopituitarism.
18
Q
most common functional pituitary adenoma?
A
prolactinoma
19
Q
symptoms of prolactinoma?
A
- infertility, lack of libido, amenorrhoea.
20
Q
second most common functional pituitary adenoma?
A
GH-secreting
21
Q
symptoms/signs of a GH-secreting pituitary adenoma?
A
- gigantism or acromegaly due to the stimulation in growth of bone/ cartilage/ connective tissue.
- increase in insulin-like growth factors.
22
Q
signs of an ACTH-secreting pituitary adenoma?
A
- Cushing’s DISEASE.
- bilateral adrenocortical hyperplasia.
23
Q
define panhypopituitarism.
A
absent/reduced anterior pituitary hormone production
24
Q
pituitary hypofunction due to sarcoidosis will show pathological features of?
A
granulomatous inflammation
25
pituitary hypofunction due to Sheehan's syndrome will show pathological features of?
infarction
26
craniopharyngioma is derived from?
remnants of Rathke's pouch.
27
a slow-growing intra-cranial tumour that is often cystic and may calcify.
craniopharyngioma
28
most craniopharyngiomas are?
suprasellar.
some arise within the sella.
29
craniopharyngiomas have a bimodal incidence of?
- 5-15 years
| - 60s-70s.
30
symptoms of craniopharyngioma?
headaches, visual disturbances.
- growth retardation in children.
31
management of cranipharyngioma?
- excellent prognosis esp. if <5cm.
| - radiation.
32
what may occur following radiotherapy for craniopharyngioma?
SCC- rarely
33
diabetes insipidus may be due to central (pituitary) causes or?
nephrogenic i.e. renal resistance to ADH.
34
SIADH is what type of syndrome?
paraneoplastic
35
how much does an adrenal gland weigh?
approx. 4-5 grams
36
where can the adrenal glands be found?
superior and medial to the upper pole of the kidneys?
37
what are the adrenal glands composed of?
outer cortex and central medulla
38
what causes hyperfunction of the adrenal cortex?
hyperplasia, adenoma, carcinoma.
39
what causes hypofunction of the adrenal cortex?
- acute: waterhouse-friederichson.
| - chronic: addison's disease
40
congenital causes of adrenocortical hyperplasia?
- autosomal recessive disorders.
| - reduced cortisol stimulating ACTH release - cortical hyperplasia (10-15x normal weight).
41
acquired causes of adrenocortical hyperplasia?
- endogenous ACTH production (cushing's disease) or ectopic ACTH (paraneoplastic syndrome e.g. SCLC).
- bilateral adrenal enlargement.
42
adrenocortical tumours most commonly affect?
male adults.
- can affect younger: Li-fraumeni syndrome.
43
adrenocortical carcinomas with necrosis may cause?
fever
44
Well circumscribed, encapsulated lesion that is small (2-3cm) with a yellow-brown surface. Cells resemble adrenocrotical cells. Can be functional, most likely not.
adrenocortical adenoma
45
Rare tumour likely to be functional and may closely resemble an adenoma. Locally invades the retroperitoneum and kidney. May haematogenously metastasise to liver/lung/bone. May spread to peritoneum, pleura and regional lymph nodes.
adrenocortical carcinoma
46
prognosis of an adrenocortical carcinoma?
5 year: 20-35% survival.
| 2 years: 50% mortality.
47
what is the only definite criteria for malignant adrenocortical tumours?
metastasis
48
features suggestive of adrenocortical carcinoma?
- large size (>50g, often >20cm).
- haemorrhage and necrosis
- frequent mitoses/atypical mitoses
- lack of clear cells
- capsular or vascular invasion.
49
Primary hyperaldosteronism otherwise known as?
Conn's syndrome
50
Usually ass. with diffuse/nodular hyperaplasia of bilateral adrenal glands.
OR
Due to adrenocortical adenoma (rarely carcinoma).
Conn's syndrome/ primary hyperaldosteronism.
51
hypercortisolism otherwise known as?
cushing's syndrome/disease.
52
exogenous causes of cushing's syndrome?
steroid therapy.
53
endogenous causes of cushing's syndrome/disease?
ACTH dependent:
- ACTH-secreting pituitary adenoma = cushing's disease. Most common.
- Ectopic ACTH e.g. small cell lung cancer.
causes adrenal hyperplasia.
ACTH-independent:
- Adrenal adenoma or carcinoma.
54
what causes acute primary adrenocortical insufficiency?
- rapid steroid withdrawal.
- adrenal crisis
- massive adrenal haemorrhage
55
what causes massive adrenal haemorrhage?
- newborn
- anti-coagulants
- disseminated intravascular coagulation
- septicaemia: waterhouse friderichsen.
56
what causes chronic primary adrenocortical insufficiency?
- addison's
- autoimmune adrenalitis
- infection (tb, histoplasma fungal, HIV, kaposi's).
- metastatic malignancy (lung, breast).
rarely: amyloid, sarcoidosis, haemochromatosis.
57
when do symptoms of chronic primary adrenocortical insufficiency present?
once >90% of the gland is destroyed.
58
addison's symptoms?
- vague: weakness, fatigue, anorexia, nausea, vomiting, weight loss, diarrhoea.
- pigmentation.
59
addison's signs?
hyperkalaemia, hyponatraemia, volume depletion and hypotension.
hypoglycaemia.
60
what may cause addison's crisis?
stress, infection, trauma, surgery.
61
how does addison's crisis present?
vomiting, abdominal pain, hypotension, shock and then death.
62
neuroendocrine (chromaffin) cells secrete?
catecholamines
63
adrenal medulla innervated by?
pre-synaptic fibres from sympathetic NS
64
tumours of the adrenal medulla?
- phaeochromocytoma
| - neuroblastoma
65
neuroblastoma usually diagnosed at what age?
18 months.
40% are diagnosed in infancy.
66
neuroblastoma typically arise in the?
adrenal medulla.
the rest usually found along the sympathetic chain.
67
what predicts poor outcome in neuroblastoma?
amplification of N-myc and telomerase expression
68
a neoplasm derived from chromaffin cells of the adrenal medulla that secretes catecholamines.
phaeochromocytoma
69
neuroblastoma are composed of primitive appearing cells, but can show maturation and differentiation towards?
ganglion cells
70
a rare cause of secondary hypertension.
phaeochromocytoma
71
what causes hypertension in phaeochromocytoma?
stress, exercise, posture, tumour palpation.
- if arising in the bladder it can be ass. with micturition.
72
complications of hypertension in phaeochromocytoma?
cardiac failure, infarction, arrhythmia, CVA.
73
how is phaeochromocytoma detected?
urinary catecholamines and metabolites
74
10% rules of phaeochromocytoma?
- 10% extra-adrenal
- 10% bilateral
- 10% malignant
- 10% NOT ass. with hypertension
- 25% are familial.
75
extra-adrenal phaeochromocytoma are known as?
paragangliomas
76
extra-adrenal phaeochromocytoma are found on the?
carotid body, organs of zuckerkandl.
77
which type of phaeochromocytoma are more likely to be malignant?
extra-adrenal i.e. paragangliomas.
78
familial cases of phaeochromocytoma more likely to present?
in younger patients, bilaterally.
79
what germline mutation increases risk of malignant phaeochromocytoma?
B-subunit of succinate dehydrogenase
80
K2Cr2O7 will cause a phaeochromocytoma to?
turn dark brown due to oxidation of catecholamines in the tumour cells.
81
phaeochromocytoma have a propensity to metastasis to where?
skeleton.
- also regional lymph nodes, liver and lung.
82
phaeochromocytoma is a feature of?
MEN2A and MEN2B
83
MEN2A is ass. with which tumours?
- phaeochromocytoma, medullary thyroid carcinoma, parathyroid hyperplasia.
84
MEN2B is ass. with which tumours?
- phaeochromocytoma, medullary thyroid carcinoma, neuromas, ganglioneuromas, marfanoid habitus.
85
zonaglumerulosa produces?
mineralocorticoids e.g. aldosterone
86
zona fasciculata produces?
glucocorticoids e.g. cortisol
87
zona reticularis produces?
sex steroids and glucocorticoids.
88
MEN1 is ass. with which tumours?
- pituitary adenoma, parathyroid hyperplasia, pancreatic tumours.
89
manifestations of Carney Complex?
- thyroid carcinoma.
- acromegaly.
- spotty pigmented sking.
- myxoma
90
tests for Carney complex?
Liddle's test: paradoxical positive response of urinary glucocorticosteroids to dexamethasone.
91
PPNAD (primary pigmented nodular adrenocortical disease) causes adrenal glands to produce excess cortisol leading to?
Cushing's syndrome
92
Carney complex due to which mutation?
PRKAR1A
93
- Cafe-au-lait skin ("coast of maine").
- polyostotic fibrous dysplasia.
- precocious puberty.
- thyroid nodules.
mccune-albright syndrome.
- pituitary: excess GH
- adrenal: cushing's
94
mccune albright syndrome due to which mutation?
GNAS1
95
- axillary freckling.
- cafe-au-lait patches
- optic gliomas
- scoliosis
- possible learning difficulties.
- rare phaeochromocytoma
NF1 - neurofibromatosis type 1
96
most common cause of primary adrenal insufficiency?
addison's disease
97
pathogenesis of addison's?
autoimmune destruction of adrenal cortex >90% destroyed before symptoms
98
what other autoimmune diseases are ass. with addison's?
- T1DM, autoimmune thyroid disease, pernicious anaemia.
99
clinical features of addison's?
- anorexia, weight loss, fatigue, dizziness, hypotension.
- abdo pain, vomiting, diarrhoea.
- skin pigmentation.
100
hyponatraemia, hyperkalaemia and hypoglycaemia are suggestive of ?
adrenal insufficiency
101
managing adrenal insufficiency?
- hydrocortisone to replace cortisol (IV if unwell): usually 15-30m/day in divided doses.
- fludrocortisone (aldosterone) needs careful monitoring of BP and K+.
102
what causes secondary adrenal insufficiency?
- exogenous steroid use.
| - pituitary/hypothalamic disease or tumours.
103
how do you differentiate between primary and secondary adrenal insufficiency?
- addison's will have pigmentation.
| - secondary lacks CRH and ACTH and will therefore be pale.
104
management of secondary adrenal insufficiency?
hydrocortisone only.
105
pale skin, normal aldosterone production but lack of CRH and ACTH.
secondary adrenal insufficiency
106
excess cortisol secretion?
cushing's
107
cushing's more common in?
women aged 20-40
108
clinical features of excess cortisol?
easy bruising, facial plethora, striae, proximal myopathy.
- buffalo hump, moon face, increased abdominal fat.
109
what is primary aldosteronism?
aldosterone production independent of its normal regulators (angiotensin II/potassium).
110
significant hypertension, alkalosis and hypokalaemia - esp. if young suggests?
primary aldosteronism
111
what are the subtypes of primary aldosteronism?
- adrenal adenoma i.e. conn's syndrome.
- bilateral adrenal hyperplasia.
- genetic mutations and unilateral hyperplasia are rare.
112
surgical management of primary aldosteronism?
ONLY FOR ADRENAL ADENOMA.
- unilateral laparoscopic adrenalectomy ONLY if adrenal adenoma (+ excess had been confirmed in adrenal vein sampling).
cures hypokalaemia and hypertension.
113
medical management of primary aldosteronism?
FOR BILATERAL ADRENAL HYPERPLASIA.
| - mineralocorticoid receptor antagonists e.g. spironolactone or eplerenone.
114
without cortisol and aldosterone replacement in adrenal insufficiency, what will happen?
death
115
bilateral adrenal hyperplasia is treated?
medically e.g. spironalactone or eplenerone.
116
adrenal adenoma is treated?
surgically
117
what is the commonest enzyme defect ass. with congenital adrenal hyperplasia?
21a-hydroxylase deficiency.
118
congenital adrenal hyperplasia is inherited by?
autosomal recessive inheritance
119
classical variant of 21a-hydroxylase deficiency?
salt-wasting and simple virilising
120
non-classical variant of 21a-hydroxylase deficiency?
hyperandrogenaemia
121
how does classical congenital adrenal hyperplasia present in males?
- adrenal insufficiency around 2-3 weeks after birth.
- poor weight gain.
- biochemical abnormalities similar to addison's: (hyperkalaemia, hyponatraemia, volume depletion and hypotension and hypoglycaemia).
122
how does classical congenital adrenal hyperplasia present in females?
genital ambiguity
123
how does non-classical congenital adrenal hyperplasia present?
- hirsutism
- acne
- oligomenorrhoea
- precocious puberty
- infertility or sub-fertility
124
paediatric management of congenital adrenal hyperplasia?
- glucocorticoid replacement.
- mineralocorticoid replacement in some.
- surgical correction.
- achieve maximal growth potential.
125
adult management of congenital adrenal hyperplasia?
- control androgen excess.
- restore fertility
- avoid steroid over-replacement
126
labile hypertension, postural hypotension, paroxysmal sweating, headache, pallor and tachycardia suggest?
phaeochromocytoma
127
complications of phaeochromocytoma?
- LV failure
- myocardial necrosis
- stroke
- shock
- paralytic ileus of bowel
128
biochemical abnormalities of phaeochromocytoma?
- hyperglycaemia (adrenaline secreting tumours).
- hypokalaemia
- raised Hb
- mild hypercalcemia
- lactic acidosis in the absence of shock
129
how do you manage phaeochromocytoma medically?
full α and β blockade - α before β!!!
- α: phenoxybenzamine.
- β: propranolol/ atenolol/ metoprolol.
- fluid +/or blood replacement.
- careful anaesthetic assessment.
- chemotherapy if malignant.
long term follow up, genetic testing + family tracing and investigation.
130
how do you manage phaeochromocytoma surgically?
laparoscopically:
- total excision when possible.
- tumour de-bulking where full removal not possible.
131
when might phaeochromocytoma levels of catecholamine be low?
- if malignant or extra-adrenal as they are less efficient at catecholamine synthesis.
- catecholamine excretion is episodic.
132
endocrine causes of hypertension?
- cushing's syndrome
- conn's syndrome
- phaeochromocytoma
133
- dehydration, confusion and polyuria (excessive thirst).
bones, groans, stones and psychic moans.
i.e. osteopenia/fractures, abdominal pain (pancreatitis, ulcers), renal stones, depression.
hypercalcaemia
134
chronic hypercalcaemia leads to?
- myopathy.
- osteopenia.
- fractures.
- depression.
- hypertension.
- abdominal pain (pancretitis, ulcers, renal stones
135
Low/normal albumin +
- high/normal PTH
- low/normal phosphate
- increased urine Ca2+ suggests?
primary or tertiary hyperparathyroidism
136
Low/normal albumin +
- high/normal PTH
- low/normal phosphate
- reduced urine Ca2+ suggests?
familial hypocalciuric hypercalcaemia (FHH)
137
Low/normal albumin +
- suppressed PTH
- high phosphate
suggests?
bone pathology
138
- hypercalcaemia
- raised albumin
- raised urea
suggests?
dehydration
139
```
Low/normal albumin +
- suppressed PTH
- high phosphate
+ low alk. phosphatase (ALP)
suggests?
```
- myeloma.
- vit. D excess
- mild alkali syndrome (thyrotoxicosis, sarcoidosis, raised HCO3)
140
```
Low/normal albumin +
- suppressed PTH
- high phosphate
+ high alk. phosphatase (ALP)
suggests?
```
- bone mets
- sarcoidosis
- thyrotoxicosis
141
what causes hypercalcaemia?
- primary or tertiary hyperthyroidism
- malignancy
- drugs: Vit. D and thiazides.
- granulomatous disease e.g. sarcoid, TB.
- FHH
- bedridden, thyrotoxicosis, pagets.
142
hypocalciuric hypercalcaemia is inherited by?
autosomal dominant inheritance
143
urine calcium excretion in hypocalciuric hypercalcaemia is?
low
- elevated serum calcium
- PTH may be elevated
144
A progressive systemic disease of the skeleton.
- low bone mass
- microarchitectural deterioration of bone tissue
- increase in bone fragility and risk of fracture
osteoporosis
145
common fracture sites in osteoporosis
- NOF
- vertebral body
- distal radius
- humeral neck
146
How many hip fracture patients die within a year of the fracture?
=20%
147
How many hip fracture patients lose the ability to live independently?
=50%
148
how much of the adult skeleton is remodelled each year?
=10%
149
In women, what causes accelerated bone loss?
menopause
- even higher risk of fragility fracture if early menopause
150
Therapeutic intervention for osteoporosis should be targeted at?
those at high risk of low impact fracture
151
Modifiable risk factors for osteoporosis fragility fractures?
- bone mineral density
- alcohol and smoking
- weight
- physical inactivity
- medications
152
what tool is used to assess fracture risk?
- Qfracture
- WHO fracture risk calculator
- FRAX
153
what important information does Qfracture not assess?
bone mineral density
154
FRAX underestimates?
risk of vertebral fracture
155
When should you assess for fracture risk?
- anyone over 50 with risk factors.
| - anyone under 50 with very strong clinical risk factors e.g. early menopause, glucocorticoid use.
156
when should you refer someone for DEXA?
anyone with a 10 year risk for any osteoporosis fracture of at least 10%
157
what is the most common method of measuring BMD?
DEXA scan
158
normal bone mineral density?
within 1 SD of the young adult reference mean
159
osteopenia bone mineral density?
more than 1 SD but less than 2.5SD below the young adult reference mean
160
osteoporosis bone mineral density?
greater than or equal to 2.5SD below the young adult mean
161
severe osteoporosis bone mineral density?
greater than or equal to 2.5SD below the young adult mean with a fragility fracture
162
lifestyle advice for management of osteoporosis?
- high intensity strength training
- low impact weight bearing exercise
- avoidance of excess alcohol
- avoid smoking
- prevent falls
163
RNI of calcium in the management of osteoporosis?
700mg/day (2-3 portions from dairy)
164
RNI of calcium in the management of osteoporosis for postmenopausal women?
1000mg/day (3-4 portions)
165
non-dairy sources of calcium?
- fortified bread and cereals
- fish with bones
- nuts, green vegetables and beans
166
drug management of osteoporosis?
- calcium and Vit. D supplements
- bisphosphonates
- denosumab
- teriparatide
- HRT
- SERMS
- testosterone
167
what do you give to reduce risk of non-vertebral fractures in those at risk of deficiency due to insufficent diet or limited sunlight exposure?
calcium and vitamin D
168
what should be advised for patients taking calcium and bisphosphonates?
calcium supplements should not be taken within 2 hours of oral bisphosphonates
169
Abnormal osteoclast activity followed by increased osteoblast activity. Result is abnormally structured bone with reduced strength and increased risk of fracture.
Paget's disease of bone
may be at a single site - monostotic
or multiple sites - polyostotic
170
which bones are predominantly affected in Paget's disease?
- long bones
- pelvis
- lumbar spine
- skull predominantly
171
- bone pain
- bone deformity (varus)
- deafness
- compression neuropathy
rarely ass. with osteosarcoma as a complication.
paget's disease
172
management of Paget's disease?
- analgesia
| - bisphosphonates if pain doesn't respond to analgesia
173
why does deafness occur in Paget's?
compression of the CN VIII (vestibulocochlear) in the bony meatus
174
Rare genetic disorders typically affecting bone secondary to type I collagen mutations. Mostly inherited by autosomal dominance.
osteogenesis imperfecta
175
May be ass. with blue sclera and dentinogenesis imperfecta.
| Type II form is neonatal lethal.
osteogenesis imperfecta
176
management of osteogenesis imperfecta?
no cure.
- fix fractures as they occur.
- correct deformities (surgery).
- bisphosphonates.
177
if suspicion of non-accidental injury, what other disease should also be considered in the differential?
osteogenesis imperfecta
178
rickets is a result of Vit. D deficiency which causes?
non-ossification of the soft osteoid resulting in bone deformity, pain and growth abnormality with widened growth plates and irregular, flared metaphyses.
179
Osteomalacia (rickets but in adults) is due to vitamin deficiency causing?
non-ossification of the soft osteoid resulting in bone deformity, pain and tendency to partial fractures with poor corticomedullary differentiation.
180
- initial lytic phase - well defined lucency.
| - later sclerotic phase - enlarged bone, increased density and coarse trabecular pattern.
paget's disease
181
what causes hypocalcaemia?
- hypoparathyroidism
- Vit. D deficiency
- chronical renal failure
- pancreatities, hyperventilation, osteoblastic bone metastases, rhabdomyolysis.
182
long term consequences of Vit. D deficiency?
- demineralisation/fractures.
- osteomalacia/rickets.
- malignancy (esp. colon)
- heart disease, diabetes.
183
management of chronic vit. D deficiency?
- vit. D3 tablets: calcitriol or alfacalcidol.
or combined calcium + Vit D.
e.g. adcal D3
184
management of vit. D -resistant rickets due to X-linked hypophosphataemia?
- phosphate
- Vit. D supplements
- +/- surgery
185
What causes primary adrenocortical insufficiency in Addison's disease?
Destruction or dysfunction of the entire adrenal cortex.
186
Describe the biochemical findings of Addison's disease.
- Hyponatraemia.
- Hyperkalaemia.
- Mild non-anion gap metabolic acidosis.
187
Loss of the adrenal gland in Addison's disease results in reduced function of which corticosteroids?
- Glucocorticoids.
| - Mineralocorticoids.
