Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Y2S2- Genetics, Renal, Endocrine > Endocrine > Flashcards

Endocrine Flashcards

You may prefer our related Brainscape-certified flashcards:
Biology 101 flashcards
1
Q

calcium homeostasis process

A
  1. detection of low plasma calcium by parathyroid gland cell
  2. release of PTH from cell by exocytosis
    also postively regulated by Vit D
    negatively regulated by calcitonin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

PTH effects on calcium and phosphate

A
  • increased bone resorption: immediate action on Ob expressing RANKL activating Oc -> bone resorption relating Ca into ECF
  • Active reabsorption of calcium and magnesium from the distal convoluted tubule. Decreases reabsorption of phosphate.
  • Increases intestinal calcium absorption by increasing activated vitamin D. Activated vitamin D increases calcium absorption
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Vitamin D effects on calcium and phosphate

A

Increases renal tubular reabsorption and gut absorption of calcium
Increases osteoclastic activity
Increases renal phosphate reabsorption in the proximal tubule

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Calcitonin effects on calcium

A

Inhibits osteoclast activity

Inhibits renal tubular absorption of calcium

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Triiodothyronine T3

A

Major hormone active in target cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Thyroxine T4

A

Most prevalent form in plasma, pro hormone

removal of iodine group by deiodinase enzymes to produce active T3

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Process of thyroid hormone synthesis

A
  1. TSH activates cAMP
  2. Trapping of iodide ions converted into iodine
  3. iodine added onto tyrosine residues on thyroglobulin by thyroid peroxidase to make diff types of thyroid hormone
  4. Colloid containing thyroglobulin resorbed into follicular cell
  5. T3 and T4 secreted
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

In blood, T4 is bound to

A

thyroxine-binding globulin (TBG) and transthyretin (TTA), with a small amount bound to albumin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

negative feedback loop of thyroid hormone

A

hypothalamus releases TRH
TRH acts on pituitary releasing TSH
TSH acts on thyroid releasing T3 and T4
T3 and T4 inhibit TSH release at pituitary and TRH release at hypothalamus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

thyroid hormone functions

A

growth development, basal metabolic rate, mental process, thermogenesis in brown adipose tissue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Causes of primary hyperthyroidism

A

Graves, toxic multi nodular goitre, thyroiditis, toxic nodule

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

toxic multi nodular goitre

A
  • multiple nodules on goitre
  • overactive nodules
    can get lid lag or lid retraction but no other thyroid eye disease features
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

thyroiditis

A

temporary overactivity of thyroid- thyroid damage & release all hormone already formed

  • followed by period of inactivity- hypothyroidism
  • trigger: preggo, infection, drugs eg. amiodarone
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Endocrine hyper(hypo)tension:

A

caused by excess (lack):

  • aldosterone from ZG
  • cortisol or precursors from ZF
  • catecholamines from medulla
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

physiological factors that control BP

A

vascular tone, ECF volume, cardiac output

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

symptoms of hyperthyroidism

A 
– Weight loss despite good appetite (often very hungry)
– Tiredness
– Tremor
– Hot, sweaty
– Palpitations
– Diarrhoea: watery
– Light/absent menses
– Mood: irritable, anxiety
– Muscle weakness
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

examination findings in hyperthyroidism

A

– Agitated, talk fast
– Warm, sweaty
– Tremor
– ­Heart Rate (HR), may be in Atrial Fibrillation (AF)
– Smooth goitre (Graves) vs MNG vs single nodule vs no goitre (thyroiditis)
– Bruit (murmur over stethoscope) heard over goitre almost diagnostic of Graves

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Graves eye signs

A 
– Redness
– Gritty sensation
– Dry or watery eyes
– Pain on eye movement
– Swelling around the eyes
– Proptosis (pushed forward appearance of eyes) – Double vision
– Loss of colour vision
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

all eye signs except _ suggest Graves

A

lid retraction and lid lag- thyrotoxicosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

thyroid function tests indications in hyperthyroidism

A

TRAbs (TSH Receptor Antibodies) significantly positive indicates Graves
– TPO (thyroid peroxidase) antibodies less specific- more in hypothyroidism
– If TRAbs are negative, do scintigraphy (often technetium rather than radio-iodine uptake

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

antithyroid drugs

A

– Carbimazole and propylthiouracil (PTU)
– Decrease production of thyroid hormone (block TPO)
– Not for thyroiditis (high T4 levels are due to release of hormone stores from damaged gland, but gland is not actually overactive)
– Rare side effect of agranulocytosis (<1/500)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

propanalol in hyperthyroidism treatment

A

good for tremor and raised HR (symptomatic)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

radioactive iodine in hyperthyroidism

A

– Risk of long term hypothyroidism
– Avoid pregnancy for 6 months.
– Restrict contact with children under 12 and pregnant women
– Don’t share bed with partner for 4 days

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

surgery in hyperthyroidism

A

– Risk of long term hypothyroidism or damage to recurrent laryngeal nerve and parathyroid glands (control calcium)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Graves eye disease mechanism

A

B cells produce TSH receptor antibodies
TSH receptor antibodies bind to TSH receptors in retro-orbital connective tissue
T cells produced inflammatory cytokine which causes swelling in muscles and tissue behind the eye= increased pressure

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

the distinction between active and inactive thyroid eye disease

A

only active disease responds to steroids

assessed with Clinical Activity Score- pain, redness, change in function, swelling

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

management of Graves eye disease

A
  • achieve euthyroidism- can have active eye disease without thyroid being overactive
  • smoking cessation
  • topical lubricants
  • selenium (antioxidant)
  • steroids and other immunosuppression
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

further steps once active eye disease settles:

A
  • elective decompression- resolve residual proptosis
  • squint surgery if EOM restriction
  • eyelid surgery if residual swelling or retraction
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

surgical decompression of the eye is done if

A

evidence of optic neuropathy and raised intraocular pressure

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

management for Graves

A

1st: ATDs

I131 or surgery for relapse

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

I131 and smoking can increase risk of

A

Graves eye disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

the initial and usually definitive imaging modality for thyroid nodule assessment

A

ultrasound

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

99mTc Pertechnetate scan nodules

A

Increased uptake/functionality – “hot” nodule

No uptake/non-functioning – “cold” nodule (more likely to be metastatic)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

I-123: imaging of active thyroid tissue

A

harmless to thyroid
determine activity of the thyroid
ectopic thyroid tissue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

When is CT/MRI used in the imaging of the thyroid?

A

Staging of suspected metastatic thyroid cancer
Assessment of metastatic thyroid cancer following treatment or on surveillance
Assessment of patients with suspected recurrence where ultrasound is negative

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

histological assessment of thyroid lesions is provided by

A

fine-needle aspiration or core biopsy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

histology vs cytology

A 
histology= solid tissue from biopsy stained, tissue architecture and cytological features
cytology= aspiration using needle and smeared onto slide
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

multi nodular goitre histology

A

dilated follicles, cholesterol clefts and foamy macrophages

produced by multiple episodes of thyroid trying to produce more product- involuting

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

Graves disease histology

A

cells have more columnar appearance, papillary architecture with scalloping

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

Hashimotos thyroiditis histology

A

Lymphoid predominant inflammation, follicular cell oncocytic change and variable degrees of gland destruction

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

Follicular adenoma histology

A

Completely encapsulated (with fibrotic tissue) lesion
Made up of thyroid follicles- collapsed colloid
Clonal population but benign

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

when does a follicular adenoma become a follicular carcinoma?

A

If capsular or vascular invasion then becomes follicular carcinoma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

what 3 features are papillary carcinomas diagnosed on?

A
  1. intraneuclear inclusions
  2. clear nuclei & nuclear irregularity
  3. nuclear grooves
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

psammoma bodies

A

laminated calcified bodies characteristic in papillary carcinoma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

Cell to colloid ratio is a good indicator of

A

malignancy, colloid is reassuring

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

key cytological features in multinodular goitre

A

lots of colloid, variably sized folloicles

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

key cytological features in papillary carcinoma

A

Papillary structures, nuclear grooves & inclusions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

key cytological features in medullary carcinoma

A

dispersed small cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

Signs of hypercalcaemia

A

Painful Bones
Renal Stones
Thrones- Constipation, Indigestion
Abdominal Groans - GI symptoms: Nausea, Vomiting,
Psychiatric Moans – Effects on nervous system: lethargy, fatigue, memory loss, psychosis, depression

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

extracellular calcium measured in either

A

serum- anti-coagulated or plasma- unclotted

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

calcium concentration is made up of 2 components, 1 of which is actively regulated:

A
  • ionised- physiologically active, actively regulated

- calcium bound to albumin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

Measuring both albumin and total calcium is required to

A

assess extracellular ionised Ca2+ status

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
53
Q

ALP function

A

promotes mineralisation by increasing the local concentration of inorganic phosphate ions
& by hydrolysing pyrophosphate, a key inhibitor of mineralisation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
54
Q

pagets disease is due to

A

overactive osteoclasts

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
55
Q

Rising Ca2+ ->

A

feeds back to the parathyroid glands and suppresses PTH secretion (negative feedback loop)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
56
Q

what is calcitonin secreted by?

A

parafollicular or C-cells of the thyroid gland

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
57
Q

Vitamin D synthesis

A

LIVER: cholecalciferol (VitD3) converted by 25-hydroxylase into 25 hydroxy-Vitamin D
KIDNEY: 25 hydroxy-Vitamin D converted by 1a- hydroxylase into 1,25 OH Vitamin D (calcetriol)- ACTIVE

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
58
Q

Renal 1α-hydroxylase is regulated by

A

PTH, calcium can affect the activity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
59
Q

mechanism of Vit D action in the intestine

A

a calcium-binding protein (calbindin- D9k) is synthesised which promotes absorption of both calcium and phosphate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
60
Q

Calcitriol limitation of action

A

Calcitriol stimulates 24-hydroxlase (promotes its own inactivation)
– Calcitriol can switch off PTH gene transcription via VDR in parathyroid cells, limiting PTH action

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
61
Q

Factitious hypercalcaemia

A

Raised [calcium] due to high plasma [albumin] e.g.

o Venous stasis o Dehydration o IV albumin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
62
Q

Primary hyperparathyroidism

presents more mildly than hypercalcemia seen in

A

malignancy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
63
Q

primary hyperparathyroidism definition and biochemical features

A

Primary - one parathyroid gland (or more) produces excess PTH. This may be asymptomatic or can lead to hypercalcaemia.
high calcium, low phosphate, mild raised ALP, PTH can be normal or high

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
64
Q

secondary hyperparathyroidism definition and biochemical features

A

Secondary - there is increased secretion of PTH in response to low calcium because of kidney, liver, or bowel disease.

low calcium, high phosphate, low Vitamin D, high PTH

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
65
Q

tertiary hyperparathyroidism definition and biochemical features

A

Tertiary - there is autonomous secretion of PTH, usually because of chronic kidney disease (CKD).
normal- high calcium, high PTH, low Vitamin D

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
66
Q

muscle contractions in hypercalcemia

A

slow muscle contractions caused by less excitable neurons secondary to hypercalcemia
- seen in primary and tertiary hyperparathyroidism

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
67
Q

Parathyroid imaging scan

A

Sestamibi- radionucleotide scan

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
68
Q

treatment of primary hyperparathyroidism

A

rehydration, drugs to lower calcium levels

removal of parathyroid adenoma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
69
Q

drugs to treat hypercalcemia

A 
o Bisphosphonates (inhibit osteoclast action and bone resorption); after re-hydration this is key drug for longer- term control
o Furosemide (inhibits distal Ca2+ reabsorption; requires care and patient must be hydrated first)
o Calcitonin (inhibits osteoclast action); tolerance may develop but useful for immediate, short-term management
o Glucocorticoids (inhibit vitamin D conversion to calcitriol; can prolong calcitonin action)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
70
Q

calcimimetics

A

bind to Ca2+ sensor and inhibit PTH release. Restricted use (e.g. parathyroid carcinomas, advanced CKD)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
71
Q

PTHrP

A

secreted by solid tumours
PTHrP shares similar actions but is distinct (PTH itself is suppressed)
• Where PTHrP is the cause= humoral hypercalcaemia of malignancy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
72
Q

how can some tumours can synthesise calcitriol?

A

haematological malignancies (esp. Hodgkin’s lymphoma) possess 1-OHase activity and synthesise calcitriol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
73
Q

multiple myeloma

A

abundance of plasma cells- protein electrophoresis helps to identify Ig type with helps management
pepper pot skull & fractures

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
74
Q

biochemical findings in malignant hypercalcemia

A

high calcium and phophate
suppressed PTH
ALP very high
GGT normal unless liver metastases

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
75
Q

FHH

A

Familial hypocalciuric hypercalcaemia- low calcium in urine but high in blood
Ca2+ sensor on parathyroid glands less sensitive to Ca2+ suppression of PTH
• Altered ‘set-point’

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
76
Q

biochemical findings in FHH

A

PTH high normal or slightly raised

plasma ionised calcium mild increase and low urine calcium excretion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
77
Q

sarcoidosis

A

small patches of red and swollen tissue- granulomatous disease
• ↑[calcium] with n[PTH]
• Hydroxylation of vit D in granulomas

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
78
Q

Chvostek’s sign

A

tapping over parotid causes facial muscles to twitch- hyperexcitability, hypocalcemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
79
Q

Trousseau’s sign

A

carpal spasm if the brachial artery occluded by inflating the blood pressure cuff and maintaining pressure above systolic
wrist flexion and fingers are drawn together- hypocalcemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
80
Q

factitious hypocalcemia

A

Consequence of low plasma [albumin] e.g.:
• Acute phase response (low albumin)
• Malnutrition or malabsorption (protein deficiency in diet)
• Liver disease (reduced liver synthesis albumin)
• Nephrotic syndrome (albumin lost in urine)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
81
Q

clinical features of vitamin D deficiency

A

Osteomalacia (defective mineralisation), symptoms related to hypocalcemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
82
Q

biochemical features of vitamin D deficiency

A 
Low 25-D3 and 1,25-D3 (usually)
• Low Ca2+ (may be normal in early stages)
• High PTH (2y hyperparathyroidism)
• Phosphate tends to be low
• Often raised ALP
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
83
Q

Causes of hypoparathyroidism

A
  • iatrogenic- accidental parathyroidectomy
  • radiation therapy
  • autoimmune
  • congenital: DiGeorge syndrome
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
84
Q

biochemical features of hypoparathyroidism

A

Low Ca2+
• Inappropriately low PTH
• Phosphate may be increased

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
85
Q

treatment of hypocalcemia

A

IV calcium in acute situations
oral calcium or Vit D
Vit D IM if malabsorption or rapid replenishment
active form if renal function impairment

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
86
Q

DEXA scan

A

assess bone mineral density, good for osteoporosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
87
Q

osteoporosis histology and biochemistry

A

normal for both

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
88
Q

loss of thirst (adipsia) can occur with

A

hypothalamic damage, this is difficult to treat- fixed fluid intake

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
89
Q

causes of polydipsia and polyuria

A

hypothalamus- primary, inhibitory/stimulatory lesions can affect this
pituitary-cranial DI, lack fo ADH
kidney- resistance to ADH (nephrogenic DI)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
90
Q

V1A receptors

A

vasopressin receptor that maintains blood volume and circulation- blood vessels

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
91
Q

V2 receptors

A

appropriate retention of water, maintain osmolality- kidney

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
92
Q

AVP receptor affinity

A

V2» V1> OT

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
93
Q

vaptans act on which receptor

A

V2 selective

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
94
Q

site of action of AVP

A

late distal tubule and collecting duct

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
95
Q

AVP mechanism

A

increase water permeability by increasing apical AQP2 (move vesicles with AQP2 to cell surface)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
96
Q

basolateral AQP3/4 on collecting duct cell

A

less sensitive than AQP2 to ADH

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
97
Q

causes of polyuria

A

DI (cranial or nephrogenic), psychogenic polydipsia, osmotic diuresis (hyperglycemia -DM), renal impairment (unusual)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
98
Q

Osmotic diuresis

A

substances that are not easily reabsorbed by the renal tubules are retained in the lumen, resulting an increase in osmotic pressure- increase in urination rate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
99
Q

water deprivation test

A 
evaluate patients who have polydipsia
Method:
prevent patient drinking water
ask the patient to empty their bladder
hourly urine and plasma osmolalities
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
100
Q

results of water deprivation test in psychogenic polydipsia

A

low starting plasma osmolality showing that the patient can concentrate their urine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
101
Q

results of water deprivation test in cranial DI

A

high starting and end plasma osmolality, low post-DDVAP plasma osmolality

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
102
Q

results of water deprivation test in nephrogenic DI

A

high starting and end plasma osmolality, high post-DDVAP plasma osmolality

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
103
Q

causes of cranial DI

A 
idiopathic
post head injury
pituitary surgery
craniopharyngiomas
histiocytosis X
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
104
Q

gestational DI

A

vasopressinase degrades AVP but not DDVAP, resolve 1w post party

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
105
Q

causes of nephrogenic DI

A
  • genetic: the more common form affects the vasopression (ADH) receptor, the less common form results from a mutation in the gene that encodes the aquaporin 2 channel
  • electrolytes: hypercalcaemia, hypokalaemia
  • lithium desensitizes the kidney’s ability to respond to ADH in the collecting ducts
  • demeclocycline
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
106
Q

treatment of cranial DI

A

central diabetes insipidus can be treated with desmopressin (DDVAP)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
107
Q

treatment of nephrogenic DI

A

thiazides (low ECF volume, increase water resorption at PCT but less at DCT), low salt/protein diet

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
108
Q

first line investigations in hyponatremia

A
  • dehydration- identify if urine is site of excess salt loss

- oedema

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
109
Q

SIADH

A

hyponatraemia secondary to the dilutional effects of excessive water retention

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
110
Q

causes of SIADH

A
  • intracranial lesions/disease- affect intracranial pathway near hypothalamus
  • intrathoracic disease esp infections- affect baroreceptor pathway: pain
  • neoplasm esp lung/mediastinal
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
111
Q

drug causes of SIADH

A 
sulfonylureas
SSRIs, tricyclics
carbamazepine
vincristine
cyclophosphamide
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
112
Q

Management of SIADH

A
  • correction must be done slowly to avoid precipitating central pontine myelinolysis
  • fluid restriction (1000ml/d to <800 if needed)
  • demeclocycline
  • ADH (vasopressin) receptor antagonists have been developed
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
113
Q

how does aldosterone deficiency (Addisons) cause hyponatremia?

A
  • Aldo reduced but ADH normal
  • non osmotic ADH stimuli: reduced vol, nausea, pain
  • reduced GC effects- impair water loss
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
114
Q

metabolic products that stimulate GH secretion

A

amino acids eg. arginine- inhibit somatostatin release

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
115
Q

demeclocycline

A

reduces the responsiveness of the collecting tubule cells to ADH

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
116
Q

GHRH- where is it synthesised and released from?

A

the arcuate nucleus, and released from neurosecretory terminals at the median eminence

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
117
Q

GHRH function

A

stimulate GH synthesis and release form stored pools

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
118
Q

somatostatin synthesised in

A

periventricular nucleus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
119
Q

somatostatin function

A

inhibits secretion of GH from somatotrophs and inhibits the secretion of GHRH

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
120
Q

GH negative regulation

A
  • glucocorticoids- initial stimulatory effect but later suppressed
  • IGF-1 and somatostatin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
121
Q

GH postitive regulation

A
  • thyroid hormone
  • catecholamines
  • ghrelin
  • oestrogen- decreased IGF-1 production
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
122
Q

hypothyroidism in childhood effect on growth

A

poor growth, blunting of GH

responses to stimuli & reduced pituitary GH levels

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
123
Q

growth hormone secretion type

A

Growth hormone secretion is pulsatile and has circadian rhythm
peak in slow wave sleep

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
124
Q

which gender has higher growth hormone secretion?

A

female

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
125
Q

GH levels in obesity

A

GH levels are lower in obesity and are restored by massive weight loss

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
126
Q

exercise and GH

A

exercise- stimulant for GH secretion, occurs around 10-15 mins after start
may be mediated by Ach, adrenaline and endogenous opioids

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
127
Q

GH signalling process

A
  1. One GH molecule binds to 2 GHR molecules leading to dimerisation of receptors
  2. Activation of receptor-associated Janus kinase, followed by STAT phosphorylation
  3. Translocates to nucleus and acts as a transcription factor
  4. Insulin-like growth factor-1 (IGF-1) gene activation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
128
Q

direct effects of GH

A
  • inhibits glycogen synthesis in muscle
  • anabolic- acts to increase blood pressure
  • increasing lipolysis and gluconeogenesis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
129
Q

indirect effects of GH

A

Most growth promoting effects of GH due to IGF-1- autocrine/paracrine effect probably most responsible fro linear growth

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
130
Q

where is IGF-1 secreted from?

A

liver and other tissue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
131
Q

what is puberty growth driven by?

A

in puberty growth is driven by GH and sex steroid, high amount of growth hormone is important in growth spurts.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
132
Q

what is childhood growth driven by?

A

GH and thyroxine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
133
Q

causes of short stature and poor growth in childhood

A 
nutrition
Chronic disease 
Genetic conditions (Turner syndrome, Trisomy 21, Noonan syndrome, skeletal dysplasias)
Steroids
Hypothyroidism
Psychosocial deprivation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
134
Q

Central causes of short stature and poor growth in childhood

A

Pituitary abnormalities

  • GH deficiency
  • TSH deficiency: hypothyroidism
  • Gonadotrophin deficiency: poor pubertal growth

These can be caused by tumours, irradiation, trauma, or genetic reasons

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
135
Q

adult GH deficiency symptoms

A

decreased energy, social isolation, depressed mood

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
136
Q

adult GH deficiency clinical features

A

increased body fat, decreased muscle mass, decreased bone density, increased risk of fracture
Impaired cardiac function
Decreased insulin sensitivity and impaired glucose tolerance

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
137
Q

what other abnormalities does adult GH deficiency present with?

A

pituitary hormone abnormalities due to new adult pituitary tumours (macroadenomas, craniopharyngiomas)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
138
Q

GH excess present before epiphyses have fused

A

gigantism

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
139
Q

GH excess present after growing ends of long bones have fused:

A

acromegaly

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
140
Q

acromegaly symptoms

A

facial change, soft tissue swelling, acral enlargement, excessive sweating, carpal tunnel syndrome, tiredness and lethargy, headaches, oligo- or amenorrhea, infertility

141
Q

why are people with acromegaly susceptible to malignancy?

A

increased GH -> increased IGF-1 -> encourage growth of malignancies

142
Q

first line treatment of acromegaly

A

transpheniodal surgery to remove tumour (may use medical therapy to shrink tumour first)

143
Q

drugs in treatment of acromegaly

A 
Somatostatin analogues (octreotide, lantreotide)
Long-acting GH receptor antagonist – pegvisomant. A modified recombinant GH molecule which prevents GH receptor dimerisation
Dopamine agonists (if concurrent high prolactin – works in <10%)
144
Q

tests of GH deficiency

A

gold standary: insulin tolerance test- hypoglycaemia stimulus for GH production

  • arginine, clonidine
  • glucagon
  • overnight GH sampling
145
Q

GH impact on insulin

A

Growth hormone has anti-insulin activity, because it suppresses the abilities of insulin to stimulate uptake of glucose in peripheral tissues and enhance glucose synthesis in the liver.

146
Q

tests of GH excess

A

glucose tolerance test

147
Q

what does the ITT show in GH deficiency?

A

lower GH peak and overall response

148
Q

what does the GTT show in GH excess?

A

GH levels should drop but it stays the same

149
Q

signs of puberty in examination of girls

A

breast staging, pubic hair, ancillary hair, acne, body habitus

150
Q

signs of puberty in examination of boys

A

testicular volumes, genital stage, pubic hair, axillary hair, acne, facial hair, body habitus

151
Q

breast buds

A

signs of estrogen production

152
Q

pubertal testicular volume

A

prepubertal= <4ml

takes 2 years to go from 4 -> 10ml

153
Q

male puberty start range and duration

A

Normal range start = 9-14 yrs

takes 5 years

154
Q

female puberty start range and duration

A

Normal range start = 8 - 13 yrs

takes 2.5 years

155
Q

compare pubertal height gain of male and female

A

male= 25 cm

female growth after menses= ~6cm

156
Q

what is adrenarche?

A

Onset of production of adrenal androgens – 2 years or more – prior to onset of puberty.
Due to maturation of adrenal cortex – zona reticularis

157
Q

clinical features of adrenarche

A

Axillary and/or pubic hair, greasy hair & skin, acne, body odour

158
Q

pathological diagnoses associated with adrenarche

A

androgen secreting tumour or late onset CAH

159
Q

slow growth and thin?
Slow growth and fat?
Rapid growth in childhood?

A
  • Chronic disease e.g Coelaic disease, IBD
  • Endocrine problem e.g. hypothyroidism
  • Sex steroid exposure e.g. precocious puberty
160
Q

central precocious puberty

A

Central activation of pubertal axis
Gonadal enlargement
Normal sequence of events

161
Q

precocious pseudopuberty

A 
Peripheral activation of sex steroids 
Not centrally activated
Incomplete pubertal sequence
No gonadal enlargement
eg. CAH, ovarian tumour
162
Q

obesity impact on growth rate

A

increased linear growth rate but don’t end up as taller adult, just get there sooner

163
Q

congenital and acquired hypopituitarism causes

A

Congenital – single or multiple pituitary deficiencies or SOD
Acquired - craniopharyngioma

164
Q

GHRH acts on

GnRH acts on

A

somatotrophs

gonadotrophs

165
Q

CRH acts on

TRH acts on

A

corticotrophs

thyrotrophs

166
Q

DA inhibits

somatostatin inhibits

A

lactotrophs

somatotrophs, thyrotrophs

167
Q

posterior pituitary hormones

A

oxytoxcin and vasopressin stored and released

168
Q

2 classes of steroid hormones

A
  • corticosteroids, glucocorticoids, adrenal androgens

- sex steroids, androgens, oestrogen, progesterone

169
Q

classical genomic mechanism of steroid hormones

A

‘Classical’ receptors in the cytoplasm activated by steroid binding - translocate to nucleus
Gene transcription & protein synthesis
Slow action

170
Q

non-genomic mechanism of steroid hormones

A

Non-classical’ receptors, activated by steroid binding, e.g. ion channels in the plasma membrane
• Intra-cellular signalling pathways, e.g. calcium/inositol
• Rapid signalling

171
Q

why are steroid hormones more water soluble than cholesterol?

A

the first step of steroid hormone synthesis in removal of the hydrophobic 6 carbon side chain

172
Q

cytochrome P450 role in steroid synthesis

A

cholesterol side chain cleavage/ modification to convert it into pregnenolone

173
Q

steroid dehyrogenases/reductase role in steroid synthesis

A

interconversion of active and inactive forms of steroid

174
Q

cortisol activation and inactivation

A

in liver and peripheral tissues

11b-HSD2 converts between cortisol and cortisone

175
Q

cortisol transport

A

bound cortisol and inactive cortisol travel to target tissues and are reactivated in target tissue

176
Q

the adrenal gland is located around the __ vertebra

A

12th thoracic

177
Q

adrenal cortex blood supply

A

arteries supply a subcapsular plexus of arterioles

• capillary sinusoids extend through the cortex separating chords of cells

178
Q

adrenal medulla blood supply

A

receives long cortical arteries & capillaries from cortex

179
Q

medulla and cortex drain via

A

the central medullary vein

180
Q

adrenocortical hormones synthesised by different parts of adrenal cortex

A

zona glomerulosa= Aldo
zona fasciculata= cortisol
zona reticularis= androgens

181
Q

what increases secretion of Aldo?

A

angiotensin II
plasma potassium
ACTH

182
Q

Aldo functions

A

Stimulates the reabsorption of sodium from the distal tubules, with a consequant excretion of potassium

183
Q

what increases secretion of cortisol?

A

ACTH from the pitutary gland, itself stimulated by CRH released by the hypothalamus
stress

184
Q

cortisol function

A
  • increases gluconeogenesis, lipolysis and proteolysis
  • Inhibits inflammatory and immune responses
  • increases insulin resistance
  • permits normal response to angiotensin II and catecholamines byup-regulating alpha-1 receptors on arterioles
  • inhibits bone formation
185
Q

what increases secretion of adrenal androgens?

A

ACTH and HPA axis

186
Q

adrenal androgen function

A

intracrine conversion to testosterone and oestradiol in peripheral tissues- external sexual characteristics

187
Q

stimulatory factors for CRH

A
  • serotonin
  • acetylcholin
  • encephalin
    ADH potentiates CRH
188
Q

inhibitory factors for CRH

A

alpha adrenergic agonists
GABA, endorphin
dopamine
cortisol

189
Q

cortisol diurnal pattern

A

high on waking 6-10am

lowest at middle of night

190
Q

how does CRH stimulate ACTH secretion from anterior pituitary corticotrophs?

A

CRH stimulates production of POMC which is then cleaved to ACTH and other peptides-> released into peripheral blood

191
Q

how is cholesterol passage across the mitochondrial lipid membrane regulated?

A

Steroid acute regulatory (StAR) protein ‘chaperones’ cholesterol across the mitochondrial membrane- rate limiting step in production of steroid hormones

192
Q

what stimulates increased StAR protein activity?

A

ANGII or ACTH stimulation

193
Q

Which hormones levels rise as plasma glucose falls?

A 
glucagon (from α cells of the pancreas) 
adrenaline
noradrenaline 
growth hormone
cortisol
194
Q

dual action of cortisol to increase plasma glucose

A

anabolic- increase liver gluconeogenesis

catabolic- proteolysis and lipolysis in peripheral muscle and fat

195
Q

difference between Cushing’s disease and syndrome

A

disease- pituitary tumour

syndrome- adrenal or ectopic tumours

196
Q

phenotype of cortisol excess

A

hypertension, hypokalaemia, high plasma cortisol, low plasma Aldo & renin activity

197
Q

difference in biochemical results between Cushing’s disease and syndrome

A

disease= high ACTH, high cortisol

syndrome (non-pituitary)= low ACTH, high cortisol

198
Q

what is renin released in response to?

A

JG cell baroreceptors
• reduced ECF & renal perfusion pressure
Macula densa cell Na+ sensing and carotid arch baroreceptors
• activates sympathetic innervation of JG apparatus

199
Q

rapid effects of RAS and aldo

A

increase vasconstriction, increase Aldo and catecholamine synthesis, increase Na and water reabsorption

200
Q

long term effects of RAS and Also

A

increased smooth cell hyperplasia and hypertrophy
increased aldo synthase enzyme expression and glomerulosa cell proliferation
increased thirst, salt appetite, ADH release

201
Q

Trophic Factors for RAS and Aldo

A

high plasma K+
low plasma Na+
Angiotensin II (RAS)

202
Q

aldosterone direct damage to heart

A

left ventricular hypertrophy, cardiac fibrosis- not consequence of hypertenison

203
Q

mineralacorticoid receptor antagonists in HF therapy

A

beneficial, blocks Aldo action in kidney and other tissues- prevent myocardial remodeller, Na retention and vascular dysfunction

204
Q

endocrine causes class as which type of hypertension?

A

secondary

205
Q

Conn’s syndrome

A

unilateral aldosterone producing adenoma

206
Q

phenotype of primary aldosteronism

A

high Aldo- MR activation:

  • hypernatremia, hypokalaemia, ECF expansion
  • hypertension, low renin
207
Q

treatment of Conn’s

A

surgical:
- venous sampling and/or CT scan then:
unilateral adrenalectomy

208
Q

Bilateral adrenal hyperplasia phenotype is the most common

A

type of primary aldosteronism

209
Q

primary aldosteronism- examples

A

Conn’s syndrome
Bilateral adrenal hyperplasia
glucocorticoid remediable aldosteronism

210
Q

treatment of Bilateral adrenal hyperplasia

A

pharmacological:

- anti-hypertensives eg. MR antagonists eg. spironolactone

211
Q

glucocorticoid remediable aldosteronism

A 
autosomal dominant (chromo 8)
ACTH driven hyperaldosteronism
212
Q

GRA hybrid gene

A

Unequal meiotic exchange 11β-OHase promoter (ACTH-driven, much more active) aldo synthase coding region

213
Q

phenotype of GRA

A

high aldosterone, MR activation,

  • high Na+, low K+, ECF expansion,
  • hypertension in neonate, low renin (RAS)
214
Q

treatment of GRA

A

suppress pituitary ACTH secretion

- synthetic glucocorticoid (Dex)- feedback and inhibit ACTH

215
Q

secondary hyperaldosteronism examples

A

renin secreting JG tumour

renal arterial sclerosis

216
Q

renin secreting JG tumour

A

renin hyper secretion- increased RAS, severe hypertension

217
Q

renal arterial stenosis

A

low perfusion pressure, renin secretion, ↑RAAS, hypertension

218
Q

phenotype of secondary hyperaldosteronism

A

high plasma renin, high aldosterone MR activation, high Na+, low K+, ECF expansion, hypertension

219
Q

treatment of renin secreting JG tumour

A

surgical removal of tumour or kidney

220
Q

treatment of renal arterial stenosis

A

anti-hypertensive, e.g. MR blockers, statins, anti-platelet agents; balloon angioplasty +/- stent

221
Q

presentation of Cushing’s syndrome/disease

A

– weight gain, stretch marks, easy bruising, proximal muscle weakness
– diabetes mellitus (high plasma glucose), menstrual irregularities, depression

222
Q

how does elevated plasma cortisol cause hypertension?

A
  • GC potentiate catecholamine action in heart & vasculature
  • inhibit vascular NO production by eNOS
  • inappropriately active kidney MR
223
Q

how does 11β-HSD-2 protect MR receptors from inappropriate activation?

A

11β-HSD-2 protects kidney MR from inappropriate activation by cortisol by converting it to inactive cortisone

224
Q

apparent MR excess

A

Autosomal recessive ‘loss of function’ mutation in 11β-HSD2

- ↓conversion of cortisol to cortisone

225
Q

conditions of GC hyperactivity

A

Cushing’s Syndrome, Cushing’s Disease, ectopic ACTH, steroids, Apparent Mineralocorticoid Excess, drugs, liquorice

226
Q

Phenotype of GC hyperactivity:

A
  • high local kidney cortisol, low RAS MR activation, high Na+, low K+ ECF expansion, hypertension
227
Q

How do drugs & liquorice ingestion cause GC excess?

A

carbenoxolone, glycyrrhizinic acid inhibitors of kidney 11β-HSD2
- ↓conversion of cortisol to cortisone

228
Q

treatment of apparent MR excess

A 
pharmacological:
MR antagonists (spironolactone, eplerenone)
229
Q

treatment of drugs & liquorice ingestion:

A

altered drug treatment

stop eating liquorice

230
Q

pheochromocytoma

A

– chromaffin cell tumour
– secrete catecholamines
– noradrenaline and/or adrenaline

231
Q

symptoms of pheochromocytoma

A

Palpitations, Headache, Episodic sweating
– racing heart, anxiety (~50%),
– hypertension – sustained/paroxysmal (~50%)
– diabetes mellitus (~40%)

232
Q

diagnosis and treatment of pheochromocytoma

A

– 24 hour urinary metanephrines & catecholamines

– α-blockers, β-blockers, surgical resection

233
Q

aldosterone renin ratio

A

both renin and aldosterone should be low in hypertension (= expected feedback)
ARR = mass concentration of aldosterone divided by plasma renin activity (recommended screening tool for primary hyperaldosteronism)
high maybe aldosterone secreting adenoma

234
Q

Patients with hypertension should always be suspected of

A

primary hyperaldosteronism

235
Q

APCCs (aldo producing cell clusters)

A

somatic mutations in genes that allow cells to depolarise and produce aldo at a lower potential

236
Q

APAs follow

A

APPCs

second hit consisting of cell proliferation and nodule formation

237
Q

Zone-specific expression of __ determines aldosterone production in the adrenal zona glomerulosa

A

aldosterone synthase

238
Q

Zone-specific expression of ___ determines cortisol production in the adrenal zona fasciculata

A

17α-OHase & 11ß-OHase

239
Q

Zone-specific expression of ___ determines DHEA production in the adrenal zona reticularis

A

17α-OHase & 17, 20 lyase

240
Q

which cytochrome P450 complexes are important in sex steroid hormone synthesis?

A
  1. 17a -OHase/17, 20 lyase (CYP17A1) - adrenal cortex ZR & testis, ovary
  2. Aromatase (CYP19A1)- convert testosterone to oestradiol
    - present in ovary AND peripheral oestrogen targets
241
Q

steroid dehydrogenase

A

interconvert steroids
• 3β-HSDs: adrenal, testis, ovary
• 17β-HSDs: testis, ovary
• 5 a-reductases: testis & peripheral tissues

242
Q

DHEA and androstenedione are made in

A

both male and female gonads

243
Q

17β-HSD3- location and function

A

found in ovaries and testes Leydig cells

converts androstenedione to weak C19 androgen testosterone that needs to be activated further in sertoli cells

244
Q

3β-HSDs

A

converts pregnenalone into progesterone in corpus luteum

245
Q

5α-reductase

A

In testis Sertoli cells 5α-reductase converts testosterone to strong androgen 5α-dihydrotestosterone

246
Q

aromatase in ovary and peripheral tissues

A

• In ovary & peripheral tissues, aromatase converts testosterone to strong oestrogen oestradiol (C18)

247
Q

sex steroid feedback loop

A

GnRH from HP preoptic nucleus

Acts on anterior pituitary gonadotrophs:
– FSH
– LH
FSH and LH stimulate sex steroid hormone production in gonads
– androgens (male),
– oestrogens (female)
– ALSO inhibins (male & female)

Hormonal feedback on pituitary & hypothalamus regulates synthesis

248
Q

Leydig and Sertoli cell role in hormone synthesis

A

Steroidogenic Leydig cells = make testosterone

Sertoli cells = ‘nursery’ cells for sperm production make inhibin & ABP (androgen binding protein)

249
Q

compartmentalisation of male sex steroid production

A

LH stimulates testosterone (T) production by Leydig cells
• FSH promotes inhibin & androgen- binding protein (ABP) in Sertoli cells
• T moves from Leydig to Sertoli cells
• T converted to DHT & binds to ABP in luminal fluid of the seminiferous tubules
T from Leydig cells & inhibin from Sertoli cells feedback on GnRH, LH & FSH

250
Q

– & – in seminiferous tubules promote sperm production & maturation

A

High testosterone & DHT

251
Q

what is testosterone bound to in plasma?

A

Testosterone transported in plasma to peripheral targets bound (98%) to
sex hormone-binding globulin (SHBG)

252
Q

androgens regulate

A

primary male repro function and secondary male sex characteristics
essential for male sex determination and genital development

253
Q

androgen insensitivity syndorme

A

46,XY
due to mutated testosterone receptor:
Arrested testis development; lack of testosterone & anti-mullerian hormone
- mullerian duct fails to regress

254
Q

partial insensitivity- androgen insensitivity syndorme

A

male external genitalia & body shape & mild spermatogenic defect after puberty

255
Q

complete insensitivity- androgen insensitivity syndorme

A

Female external genitalia & body shape, female internal organs undeveloped or absent

256
Q

natural mutation in the aromatase gene leads to

A

failure to convert testosterone to oestradiol

257
Q

oestrogen deficiency affects

A

bone maturation:
– tall and long arms
– bone epiphyses did not close – Loss of bone mass
– osteoporosis

258
Q

compartmentalisation of female sex steroid production

A

LH stimulates production of androstenedione & testosterone in thecal cells of the primary follicle
• Androgens move from thecal to granulosa cells
• FSH stimulates androgen conversion to estrogens by aromatase
Estradiol & inhibin from granulosa cells feed back on GnRH + LH & FSH release from HP & pituitar

259
Q

– regulates the proliferative phase of the female menstrual cycle

A

oestradiol

260
Q

what is oestradiol bound to in plasma?

A

SHBG

261
Q

what can increased SHBG lead to?

A

lower free sex hormone availability

262
Q

role of oestrogen

A

Female genital development & differentiation
• Secondary female sex characteristics
Estrogen from the primary ovarian follicle promotes endometrial growth during the follicular or ‘proliferative’ phase

263
Q

role of progesterone

A

Made in the corpus luteum promotes endometrial secretion & vascularisation during the luteal or ‘secretory’ phase
• Prepares uterus for implantation of a fertilised egg
• Without implantation falling progesterone initiates menstruation

264
Q

luteal-placental shift in pregnancy

A

Hormones decline: hCG from embryo & progesterone from corpus luteum
To maintain pregnancy, placenta begins to produce:
progesterone from cholesterol and oestrogen from DHEA (fetal adrenal)

265
Q

causes of Addison’s disease

A

primary adrenal insufficiency- destruction of adrenal gland by tuberculosis, cancer metastases, autoimmune disease

266
Q

why does skin pigmentation occur in Addisons?

A

high ACTH binds to a-MSH receptor on melanocytes (agonist)

267
Q

presentation of Addisons

A

symptoms of all adrenocortical zones
- hyperpigmentation, hypotension, extreme fatigue,
weight loss and decreased appetite, hypoglycaemia, salt craving, abdominal pain

268
Q

phenotype of Addison’s

A

low plasma aldo= lack of MR activation

  • low Na+, high K+, reduced ECF, hypotension,
  • Low plasma cortisol, low glucose, high ACTH (lack of cortisol feedback)
269
Q

treatment of Addisons

A 
Fluid & hormone replacement
synthetic glucocorticoid (hydrocortisone, prednisone) synthetic mineralocorticoid (fludrocortisone)
270
Q

Hypopituitarism- secondary adrenal insufficiency causes

A
  • partial or complete loss of anterior lobe pituitary function
  • tumour, pituitary apoplexy, suppression by long-term corticosteroids - lack of pituitary ACTH secretion & adrenocortical trophic stimulation
271
Q

presentation of hypopituitarism

A

malfunction of ZF & ZR, reduced cortisol & androgen secretion

  • RAS and Aldo secretion largely unaffected
  • same as for Addison disease and include fatigue, weakness, weight loss, nausea, vomiting, and diarrhea, but there is usually less hypovolemia
272
Q

phenotype of hypopituitarism

A
  • low plasma ACTH & cortisol due to pituitary & adrenal failure - Increased vasopressin release from posterior pituitary
  • ECV expansion low Na+, low K+ (dilutional hyponatraemia)
273
Q

treatment of hypopituitarism

A
  • hormone replacement, transsphenoidal decompression/tumour removal - synthetic glucocorticoid (hydrocortisone, prednisone), thyroxine, etc.
274
Q

what is congenital adrenal hyperplasia?

A

Inherited condition present at birth (congenital) in which the adrenal gland is larger than usual (hyperplasia)
form of primary adrenal insufficiency
Usually caused by an inherited defect in gene for any steroidogenic enzyme
Inactivating mutations partial or complete

275
Q

inheritance of CAH

A 
Autosomal recessive (both parents carriers)
Heterozygote ‘carriers’ usually asymptomatic (may affect immune system)
276
Q

genotype of CAH affected individuals

A

Affected individuals usually compound heterozygotes:
both alleles altered, but different mutations inherited from mother & father
Genuine homozygotes seen from consanguineous marriage

277
Q

most common type of CAH

A

steroid 21-hydroxylase (90-95%)

278
Q

21-OHase pseudogene

A

actually 2 genes but 1 has been inactivated and non functional- in meiosis mutations can be swapped into the functional one

279
Q

less common types of CAH

A

11b hydoxylase
17a hydroxylase
3b-HSD
StAR

280
Q

StAR lipoid CAH

A

fat imported into the cytoplasm of adrenocortical cell but can’t be imported across mitochondrial membrane where steroid are made
accumulating fat= lipotoxic

281
Q

presentation in all CAH syndromes

A

block in cortisol synthetic pathway: reduced cortisol, plasma glucose and feedback on CRH-ACTH
elevated ACTH: adrenal stimulation and hyperplasia
intermediate accumulation and reduced hormone

282
Q

which intermediates would accumulate after the block in 21-hydroxylase pathway?

A

reduced cortisol and Aldo with increased ACTH

increased progesterone and 17 a-OH progesterone, increased DHEA and androstenedione

283
Q

diagnosis of CAH

A

Usually soon after birth
Less severe CAH not apparent until puberty
Prenatal diagnosis possible now affected genes identified

284
Q

effects of partial inactivation of 21-hydroxyl CAH

A

↓ Cortisol, ↓ feedback, ↑ACTH
Symptoms reflect mainly a lack of cortisol (enough aldo still made)
• Increased androgens
– virilisation in boys; masculinisation in girls

285
Q

why are there fertility problems in complete 21-hydroxylase CAH?

A

increased DHEA and androstenedione lead to increased feedback on pituitary-> reduced LH and FSH

286
Q

most common cause of ambiguous genitalia is

A

due to prenatal masculinaisation of genetical female infants

287
Q

treatment of partial block 21-OH CAH

A 
– replace cortisol function
– feed-back inhibit ACTH ‘drive’
– reduce ACTH-driven androgens
Monitoring:
– glucocorticoid replacement
– monitor 17-OH progesterone and androgens
288
Q

treatment of complete block 21-OH CAH

A 
– replace cortisol & mineralocorticoid
– reduce ACTH-driven androgens
– normalise plasma Na+, ECF & bp
Monitoring:
– glucocorticoid & mineralocorticoid
– monitor 17-OH progesterone and androgens
289
Q

untreated 21-OH CAH left untreated in females

A

ambiguous genitalia
single urethral/vaginal orifice (no separation)
fused labia & enlarged clitoris

290
Q

late onset 21-OH CAH

A

mild inactivating mutation – less severe than in affected neonates
– usually presents after puberty in women
– following upsurge in ACTH & adrenal steroid secretion (adrenarche)

291
Q

excess adrenal androgen results in

A

PCOS, hirsutisme, infertility

292
Q

treatment of late onset 21-OH CAH

A

hydrocortisone replacement: titrate GC replacement

monitor 17-OH progesterone and androgen levels

293
Q

hormonal pattern in 11b-OH CAH

A

reduced/no cortisol (partial), increased ACTH

increased substrates: deoxycortisol and DOC in ZF and excess adrenal androgens

294
Q

why can hypertension present in 11-OH CAH?

A

hypertension due to weak MR activity of DOC at MR receptor

clinical clue that patient has 11OH-CAH instead of 21-OH CAH

295
Q

treatment of 11-OH CAH

A

lifelong glucocorticoid replacement
monitor 17-OH progesterone & androgen levels
• also measure plasma Na+ concentration

296
Q

symptoms in Addisonian crisis

A

Reduced consciousness
Hypotension
Hypoglycaemia, hyponatraemia, hyperkalemia
Patients can be very unwell

297
Q

Primary Addison’s is associated with – whereas secondary adrenal insufficiency is not

A

hyperpigmentation

298
Q

Chromogranin A

A

widely accepted biomarker for the assessment of neuro-endocrine tumors

299
Q

Synaptophysin

A

integral part of the neuroendocrine secretory granule membrane
recognised by monoclonal antibody in NET (pathology)

300
Q

flushing and diarrhoea are signs of

A

hormonal excess

301
Q

carcinoid syndrome

A

collection of symptoms some people get when a neuroendocrine tumour, usually one that has spread to the liver, releases hormones such as serotonin into the bloodstream

302
Q

how is serotonin measure?

A

serotonin itself can’t be measured so 5HIAA must be measured in 24h urine collection

303
Q

serotonin causes the symptoms:

A

flushing, diarrhoea, acute bronchospasm, right heart failure- serotonin sticks to 5HT receptors on heart valves

304
Q

why does serotonin cause right heart disease?

A

serotonin is usually cleared in the enterohepatic circulation but liver disease overrides the enterohepatic circulation allowing serotonin to get into right heart

305
Q

what aspects of right heart disease does serotonin cause?

A 
valve fibrosis
RHF
elevated JVP
peripheral oedema 
hepatic congestion
306
Q

‘pulsatile liver’

A

tricuspid regurgitation as result of valve fibrosis and if really bad then can be felt in liver

307
Q

Clinical characteristics of NETs

A 
Rare
• Significant majority arise in GI system (including pancreas)
• Usually slow growing
• Wide spectrum of disease activity 
• Often metastatic at presentation
• Prolonged survival is possible
308
Q

presentation of liver NETs

A

liver → present w/ pain from enlargement of capsule, abnormal LFTs

309
Q

presentation of large/small bowel NETs

A

terminal ileum if tumour is in large/small bowel → bowel obstruction
↳ abdominal distention, vomiting

310
Q

presentation of pancreatic NETs

A

usually picked up on CT- abdominal pain

311
Q

presentation of stomach NETs

A

iron deficiency anemia- blood loss, indigestion

312
Q

hormonal presentation of pancreatic NET

A 
increased:
insulin- hypoglycemia
glucagon- diabetes and usual rash
gastrin- heartburn, pectin ulcers
VIP- diarrhoea (profuse, watery, hypokalemia
313
Q

treatment options for NETs

A

active surveillance
surgery (bowel/ pancreatic/ hepatic)
somatostatin analogue therapy
radionucleotide therapy

314
Q

when is radionucleotide therapy useful for NETs?

A

symptom control when SA no longer fully effective

can target relatively ischaemic central core of metastatic deposits

315
Q

transarterial chemoemolisation

A

deprive mass of blood supply
only targets cancer deposits in liver
destructive therapy so potential for rapid release of hormones from dying cells

316
Q

MEN type 1 mutation

A

defect in MEN1 gene- menin

tumour suppressor gene

317
Q

MEN inheritance

A

autosomal dominant

318
Q

Clinical features of MEN type 1

A

Parathyroid (95%): hyperparathyroidism due to parathyroid hyperplasia
Pituitary (70%)
Pancreas (50%): e.g. insulinoma, gastrinoma (leading to recurrent peptic ulceration)

Also: adrenal and thyroid

319
Q

screening of MEN1

A

Annual calcium and PTH
• Annual fasting gut hormones
– Chromogrannin A, insulin-glucose, gastrin glucagon, pancreatic polypeptide
• 3 yearly MRI of pituitary and now pancreas
• Consideration for CT / MRI of chest and thymus

320
Q

MEN type 2

A

defect in MEN2 producing ret- proto-oncogene gene

321
Q

Clinical features of MEN type 2A

A

Medullary thyroid cancer (70%)
Parathyroid (60%)
Phaeochromocytoma

322
Q

Pheochromocytoma crisis

A

increased adrenaline leading to heart attack and multi organ failure

323
Q

Clinical features of MEN type 2B

A 
Hyperparathyroidism
Medullary thyroid cancer
Phaeochromocytoma
Marfanoid body habitus
Neuromas, musculoskeletal abnormalities (tall, thin)
324
Q

Most common presentation of MEN1

A

hypercalcemia

325
Q

how does glucocorticoid deficiency cause hyponatremia?

A

reduced GC effects- impair water loss
central effect- body retains more water
renal effect- reduced renal water excretion
reduced glucose is a non-osmotic ADH stimulus
DILUTIONAL HYPONATREMIA

326
Q

triple phase response after pituitary surgery

A

early diabetes insipidus dipping into SIADH and then return of diabetes insipidus

327
Q

reasoning behind triple phase response following pituitary surgery

A

level of hypothalamus-pituitary damage
AVP neurones may recover posterior pituitary- temp DI
partially processed forms released from pituitary stalk- SIADH
AVP neurones die quickly in hypothalamus- permanent DI

328
Q

leptin production and action

A

It is produced by adipose tissue and acts on satiety centres in the hypothalamus and decreases appetite.

329
Q

Leptin stimulates the release of

A

melanocyte-stimulating hormone (MSH) and corticotrophin-releasing hormone (CRH)

330
Q

Low levels of leptin stimulates the release of

A

neuropeptide Y (NPY)

331
Q

ghrelin is produced by

A

the P/D1 cells lining the fundus of the stomach and epsilon cells of the pancreas

332
Q

ghrelin levels

A

increase before meals and decrease after meals

333
Q

causes of secondary obesity

A

Hypothyroidism
• Cushing’s syndrome - usually iatrogenic
• Hypothalamic disease
• Others
› Drugs (oestrogen, beta blockers, tricyclic antidepressants, sodium valproate)
› Insulinoma, GH deficiency Genetic Disorders: e.g. Prader Willi syndrome

334
Q

thyroxine deficiency is characterised by which fat distribution?

A

generalised

335
Q

which hormonal abnormalities can lead to apple shaped fat distribution?

A

androgen and cortisol excess

GH deficiency

336
Q

which hormonal abnormalities can lead to pear shaped fat distribution?

A

oestrogen excess

337
Q

leptin in obesity

A

leptin resistance in obesity- no signal to tell you that you’re full

338
Q

what is the overnight dexamethasone suppression test?

A

using synthetic glucocorticoid to suppress pituitary ACTH secretion & cortisol production from adrenal cortex (negative feedback)

339
Q

low dose dexamethasone suppression test

A

suppresses pituitary ACTH secretion and cortisol production in normal individuals, but not from a pituitary adenoma (Cushing’s Disease)

340
Q

high dose dexamethasone suppression test

A

part-inhibits ACTH secretion from a pituitary adenoma, but not from a cortisol-producing adrenal adenoma or an ectopic ACTH-producing tumour (Cushing’s syndrome)

341
Q

What is the synacthen test?

A

quantifies adrenal function or lack of function (insufficiency)

342
Q

short synacthen test

A

synthetic ACTH will stimulate healthy adrenal glands to produce cortisol and the cortisol level should at least double. A failure of cortisol to rise (less than double the baseline) indicates primary adrenal insufficiency (Addison’s disease).

343
Q

long synacthen test

A

In primary adrenal failure there is no cortisol response as the adrenals no longer function.
In adrenal atrophy (secondary adrenal insufficiency), the prolonged ACTH eventually gets the adrenals going again and cortisol rises.

344
Q

triggers of Addisonian crisis

A
  • can be the first presentation of Addisons Disease
  • triggered by infection, trauma or other acute illness in someone with established Addisons.
  • can present in someone on long term steroids suddenly withdrawing those steroids.
345
Q

Rotterdam criteria

A

for PCOS
anovulation, elevated levels of androgenic hormones, and/or enlarged ovaries containing at least 12 follicles each- transvaginal USS

346
Q

DIDMOAD is

A

the association of cranial Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy and Deafness (also known as Wolfram’s syndrome)

347
Q

damage to the pituitary stalk can lead to

A

cranial diabetes insipidus

stops the transport of oxytocin and vasopressin

348
Q

what can impair t4 absorption?

A

PPIs eg omeprazole/lansoprazole
H2 antagonists eg ranitidine
Iron, calcium, aluminium
Don’t take T4 <4h after these

349
Q

Increased T4 requirement if

A

start oestrogen (OCP, HRT) or anticonvulsants

Y2S2- Genetics, Renal, Endocrine (6 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions