Week 15 Flashcards
(145 cards)
1
Q
What is the definition of diabetes?
A
a metabolic disorder of multiple aetiology characterised by chronic hyperglycaemia with disturbances of carbohydrate, protein and fat metabolism resulting from defects in insulin secretion, insulin action or both
2
Q
Describe the WHO criteria for the diagnosis of diabetes
A
fasting plasma glucose >7mmol/L
random plasma glucose of >11.1
one abnormal value diagnostic if symptomatic
2 abnormal values diagnostic if asymptomatic
HbA1c 6.5% or 48mmol/mol
diabetes should not be diagnosed on the basis of glycosuria or a BM stick
OGTT only required if IFG of GDM
3
Q
What are the main presentations of diabetes?
A
glyocosuria glucose shifts ketone production depletion of energy stores complications (T2DM)
4
Q
Describe glycosuria
A
tired, weak, weight loss, difficulty concentrating, polyuria, polydipsia, dry mucous membranes, reduced skin turgor, postural hypotension
5
Q
Describe glucose shift
A
swollen ocular lenses leading to blurred vision
6
Q
Describe effects of ketones production
A
nausea vomiting abdominal pain heavy/rapid breathing acetone breath drowsiness coma
7
Q
Describe depletion of energy stores
A
weakness
polyphagia
weight loss
growth retardation in young
8
Q
Give overview of T1DM
A
age <20 lean symptoms weeks northern european HLA DR3/DR4 autoimmune ketonuria insulin deficiecny / ketoacidosis/ dependent on insulin for survival peptide C inappropriate /negative
9
Q
Give overview of T2DM
A
>30 overweight months / years asian, african, polynesian and american indian no HLA links no ketones partial insulin deficiency, hypoerosmolar state C peptide positive
10
Q
Describe islet autoantibodies
A
markers of autoimmune process associated with T1Dm
glutamic acid decarboxylase and insulinoma associated antigen
11
Q
Describe C-peptide
A
secreted in equimolar concentrations to insulin
marker of endogenous insulin secretion
most usuful 3-5 years from onset
can be measured in blood or urine
12
Q
Describe the pathogenesis of type 1 diabetes
A
chronic progressive metabolic disorder characterised by hyperglycaemia and the absence of insulin secretion
type 1 diabetes results from autoimmune destruction of the the insulin producing beta cells in the islets of langerhans
occurs in genetically susceptible subjects and is probably triggered by one or more environmental agents
13
Q
What are some of the potential triggers of T1DM?
A
viral infections immunisations diet higher socio-economic status obesity vitamin D deficiency perinatal factors
14
Q
Describe the pathogenesis of Type 2 DM
A
chronic progressive metabolic disorder characterised by hyperglycaemia, insulin resistance and relative impairment of insulin deficiency
common with a prevalence that rises markedly with increases levels of obesity
most likely arises through a complex interaction among many genes and environmental factors
15
Q
What does MODY stand for?
A
maturity onset diabetes of the young
16
Q
Describe MODY
A
caused by a change in a single gene. Autosomal dominant
often <25 years
runs in families in each generation
managed by diet, OHAs, insulin (not always)
17
Q
Describe gestational diabetes
A
carbohydrate intolerance with onset, or diagnosis during pregnancy
risk factors include high BMI, previous macrosomic baby or gestational diabetes, family history or ethnic prevalence of diabetes
18
Q
Describe screening and diagnosis of gestational diabetes
A
all women with risk factors should have an OGTT at 24-28 weeks.
fasting venous plasma glucose >5.1
one hour - >10
2 hours >8.5
19
Q
What are the causes of secondary diabetes?
A
genetic defects of beta cell fucntion
genetic defects in insulin action
disease of exocrine pancreas- pancreatitis/ carcinoma/CF/haemochromatosis
endocrinopathies - acromegaly/cushing’s , phaeo
immunosuppressive agents - glucocorticoids, tacrolimus, ciclosporin
anti-psychotics - cloazpine/onlazipine
genetic syndromes associated with DM - Down’s syndrome, friedreich’s ataxia. turners, myotonic dystrophy, kleinfelter’s syndrome
20
Q
What are the layers of the adrenal cortex?
A
glomerulosa
fasiculata
reticularis
21
Q
What does the zone glomerulosa produce?
A
aldosterone
22
Q
What does the zone fasiculata produce?
A
cortisol
23
Q
What does the zone reticularis produce?
A
androgens
24
Q
What sort of cells are found in the adrenal medulla and what do they produce?
A
chromograffin cells
catecholamines
25
Describe the regulation of the renin-angiotensin system
renin major regulator of aldosterone production
activated in response to decreased blood pressure
leads to production of angiotensin II which causes vasoconstriction and aldosterone production, both of which raise blood pressure
26
Describe the action of aldosterone
binds to mineralocorticoid receptor and causes increased absorption of sodium (and water) and increased potassium secretion
27
Describe the regulation of cortisol / androgen production
illness, stress time of day - release of corticotropin releasing hormone
anterior pituitary releases adrenocorticotropic hormones which causes the adrenal cortex to produce cortisol (and androgens)
28
When is a secondary cause of hypertension more likely?
young
resistant / severe hypertension
clinical suspicion - hypokalaemia
29
What tests are used to investigated aldosteronism?
aldosterone (high)
renin (low)
aldosterone, renin ration (high)
30
What are the causes of primary aldosteronism?
adenoma
| bilateral hyperplasia
31
Describe the confirmation of aldosterone excess
stop beta blockers and MR antagonists
Saline suppression test - 2L saline over 4 hours
4h aldosterone >270 highly suspicious
32
Describe the management of primary aldosteronism
```
Surgical
unlilateral laparoscopic adrenalectomy
(only if adenoma)
cure hypokalaemia
cures hypertension in 30-70% of cases
```
```
medical
use MR antagonists (spironalactone or eplerenone)
or amiloride (blocks Na reabsorption by kidney)
```
33
What are common signs and symptoms of cushings syndrome?
```
weight gain
hirsutism
psychiatric
proximal myopathy
obesity - trunk/generalised
plethora
moon face
hypertension
brusing
striae
buffalo humo
poor wound healing
avascular necrosis of femoral head
osteoporosis
insulin resistance
increased appetite
infection
```
34
Describe screening for cushing's syndrome
urinary free cortisol (X3 cortisol:creatinine ration or 24 hour urine collection cortisol)
dexamethasone suppression test (plasma cortisol should be undetectable in normal circumstances )
late night salivary cortisol - should be very low or undetectable normally
35
What are the causes of ACTH dependent cushings?
```
pituitary adenoma (Cushing's disease)
ectopic ACTH (cancer)
ectopic CRH (rare)
```
36
What are causes of ACTH independent cushings?
adrenal adenoma
adrenal carcinoma
nodular hyperplasia
37
Describe the tests used to localise the cause of cortisol excess
plasma ACTH
high dose dexamethasone suppression test
CRH test
imaging
38
Describe high dose dexamethasone suppression test
if pituitary, cortisol will suppress to <50%
| no response to ectopic ACTH
39
Describe CRH test
exaggerated response in pituitary disease
| no response to ectopic ACTH
40
Describe imaging in Cushing's disease
adrenal CT or MRI
pituitary MRI (only detects 50% of ACTH producing pituitary tumours)
optimal imaging for ectopic tumours unclear (CT/PET/MRI)
41
Describe congenital adrenal hyperplasia
```
autosomal recessive disorder
range of genetic disorders relating to defects in steroidogenic genes
most common CYP21 (21 alpha hydroxylase)
females - ambiguous genitalia
boys -adrenal crisis, early virilisation
```
treated with mineralocorticoid and glucocorticoid replacement
42
Describe phaeochromocytoma
usually in adrenal medulla
paraganglioma - extra-adrenal neural crest cells
symptoms /signs
hypertension
episodes of headache, palpitations, pallor and sweating
also tremor, anxiety, nausea, vomiting, chest or abdominal pain
crises last 15 minutes
often well in between
43
Describe the diagnosis of pheochromocytoma
```
24 hour urinary catecholamines (atleast twice)
imaging - CT abdomen
MIGB scan (chromatin seeking analogue)
```
44
What genetic conditions are associated with pheochromocytoma?
MEN
VHL
SDHB and SDHD
neurofibromatosis
some are malignant and have poor prognosis
45
Describe the pre-operative treatment of pheochromocytoma
alpha blockade initially
Then beta blocker if tachycardic
encourage salt intake
46
Describe adrenal insufficiency
inadequate adrenocorticol function
primary - Addison's, autoimmune destruction
```
clinical features
anorexia, weight loss
fatigue / lethargy
dizziness and low BP
abdominal pain, vomiting and diarrhoea
skin pigmentation
```
47
Describe the diagnosis of adrenal insufficiency
suspicious biochemistry (low sodium, high potassium, hypoglycaemia)
short synacthen test
ACTH levees
renin aldosterone levels
adrenal autoantibodies
48
Describe the short SYNACTHEN test
measure plasma cortisol before and 30 minutes after IV ACTH injection
normal:baseliin >250, post ACTH >480
49
Describe ACTH levels in primary adrenal insufficiency
should be very high
| causes skin pigementation
50
Describe the renin and aldosterone levels in primary adrenal insufficiency
very high renin
| very low aldosterone
51
Describe the management of primary adrenal insufficiency
do not delay treatment to confirm diagnosis
hydrocortisone as cortisol replacement - if unwell give IV first
usually 15-30mg day in divided doses
try to mimic diurnal rhythm
fludrocortisone as aldosterone replacement - careful monitoring of BP and K
need education - sick day rules, cannot stop suddenly, must wear ID
52
What is non-diabetes related hypoglycaemia?
an uncommon cause of symptoms in adults, except in those with DM treated with glucose-lowering meds
53
What is the non DM plasma glucose level classified as hypoglycaemia?
<2.8
54
What are the autonomic symptoms of hypoglycaemia?
sweating, palpitations, pallor, tremors, nausea, irritability, hunger
55
What are the neuroglycopenic symptoms?
inability to concentrate, confusion, drowsiness, personality change, slurred speech, incoordination, weakness, dizziness, vision impairment, headache, seizures, coma
56
What is Whipple's triad?
symptoms consistent with hypoglycaemia
low plasma glucose concentration
relief of those symptoms after the plasma glucose has raised
57
What is important to ascertain in the history about hypoglycaemia
Does WHipples triad exist?
Ensure that there is definite evidence of a low glucose level (must be venous blood)
Do symptoms occur in the fasting or post-prandial state?
Take a full past medical history, family history and drug history
58
Describe the Investigations for hypoglycaemia
```
Post prandial investigations - mixed meal test
72 hour fast
glucose
insulin
C peptide
SU screen
Beta hydroxybutyrate low in insulinoma
Pro-insulin low with exogenous insulin
insulin antibodies
```
59
Describe the 72 hour fast in the investigation of hypoglycaemia
provoke the homeostatic reponse that keeps blood glucose concentrations from falling to concentrations that cause symptoms in the absence of food
Glucagon, adrenaline > GH/cortisol are the most important components
complete at plasma glucose at 2.5, 62 hours have elapsed or when plasma glucose is <3 if Whipple's triad previously documented
young, lean, healthy women may have plasma glucose ranges of 2.2 or even lower after prolonged periods of fasting
60
Describe localising studies in the investigation of hypoglycaemia
Radiology - CT, MRI, EUS
arterial calcium stimulation - distinguishes focal from diffuse disease
61
What are causes of spontaneous hypoglycaemia?
```
pancreatic - insulinoma, non insulin pancreatogenic hypoglycaemia
non islet cell tumour hypoglycaemia
autoimmune
reactive hypoglycaemia
drug induced
dietary toxins
organ failure
endocrine disease
inborn errors of metabolism
sepsis
starvation
anorexia
total parenteral nutrition
severe excessive exercise
```
62
What drugs can cause hypoglycaemia?
```
insulin
sulphonylureas
repaglinide
salicylates
quinine
hapoperidol
beta blockers
indomethacin
lithium
levofloxacin
heparin
trimethoprim
pentamidine
disopyramide
```
63
How should an ill or medicated individual be investigated for hypoglycaemia?
drugs
critical illness
hormone deficiency - cortisol
non islet cell tumour
64
how should a seemingly well individual be investigated for hypoglycaemia?
endogenous hypoerinsulinsim - insulinoma, functional islet cell disorders, insulin autoimmune hypoglycaemia
accidental, surreptitious, malicious hypoglycaemia
65
Give examples of congenital abnormalities in mullerian development
isolated defect androgen insensitivity syndrome
5-alpha reductase deficiency
vanishing testes syndrome
defect in Sry gene
66
Give examples of congenital defects or urogenital sinus development
agenesis of lower vagina
| imperforate hymen
67
What hormones increase and decrease hypothalamus secretion of GnRH?
leptin increases
| ghrelin decreases
68
What is important in the investigation of oligomenorrhoea?
```
HCG
history - weight change, exercise, illness
galactorrhea
drugs - dopamine agonists
hot flushes, vaginal dryness, libido
hirsutism
```
examination - BMI, acanthuses, hirsutism, acne
dental erosions
bloods - FSH, LH oestrogen, SHBG, testosterone, prolactin, TSH, fT4
69
What is the differential diagnosis for oligomenrrohea and androgenisation of a female?
PCOS
congenital adrenal hyperplasia
Cushing's
virilising tumours
70
What additional tests can be carried out for investigation of oligomennorhea and androgenisation?
progesterone (early morning)
USS ovaries
overnight 1mg dexamethasone suppression (of features of Cushing's)
71
Describe PCOS
heterogeneous disorder of unclear aetiology
| complex interaction of metabolic, hypothalamic, pituitary, ovarian an adrenal mechanisms
72
What is the definition of PCOS?
clinical and / or biochemical signs of hyperandrogenism
| oligo- and or anovulation
73
Describe the pathophysiology of PCOS
increased insulin secretion to given glucose load
insulin stimulates ovarian thecae cells to produce androgens
insulin reduces hepatic SHBG
increase free testosterone
oligo-ovulation, hirsutism,
74
What are the long term consequences of PCOS?
T2DM
dyslipidaemia
cardiovascular disease
endometrial hyperplasia
75
What pharmacological treatment is available for PCOS?
ovarian androgen suppression - OCP. dianette
adrenal androgen suppression - glucocorticoid
androgen receptor antagonist - spironalactone
5 alpha reductase inhibition - finasteride / spironalactone
topical inhibitors - eflornithine
76
Describe the secretion and regulation of growth hormone
growth hormone releasing hormone is released by the hypothalamus
growth hormone is released by the anterior pituitary by somatotrophs
it acts on multiple target organs
77
What are all the names of ADH?
AVP
vasopressin
arginine vasopressin
argipressin
78
Describe hypopituitarism
failure of (anterior) pituitary function
can affect single hormonal axis or all hormones
Leads to secondary gonadal / thyroid/ adrenal failure
need multiple hormone replacement
79
What can cause hypopituitarism?
```
tumours
radiotherapy
infarction / haemorrhage
- associated headache / visual disturbance
assoc pPH (sheehan's syndrome)
Infiltration (sarcoid)
trauma
lymphocytic hypophytis
```
80
Describe anterior pituitary hormone replacement
```
ACTH - hydrocortisone
TSH - thyroxine
FSH / LH - testosterone / oestrogen
GH - growth hormone
PRL - no replacement
```
81
What are causes of high prolactin?
prolactinomas
physiological - lactation / pregnancy
drugs - tricyclics / antiemetics / antipsychotics
Stalk effect - due to loss of inhibitory dopamine
82
What are the main types of pituitary tumours?
```
Non-functioning (majority)
functioning - prolactin
GH (acromegaly)
ACTH (cushing's disease)
TSH ( TSHoma)
```
others - craniopharyngioma, pituitary cancer, Rathke's disease
83
Describe non- functioning pituitary tumours
commonest
no hormonal release
but cause problems - visual field defects
headache
stops other pituitary hormones working
eye morvement problems
84
Describe the investigation and treatment of non- functioning pituitary tumours
Investigation - imaging
visual field assessment
prolactin
other pituitary hormones
treatment -
surgery
RT
medical management is unhelpful
85
Describe prolactinomas
pituitary tumours releasing prolactin
```
clinical features
galactorrhoea
headaches
mass effect
visual field defect
amenorrhoea / erectile dysfunction
```
86
Describe the diagnosis of prolactinomas
serum prolactin usually >6000
MRI pituitary
Test remaining pituitary function - gonadal function and thyroid hormones most effected
87
Describe the treatment of prolactinomas
medical - dopamine agonists
cabergoline / bromocriptine / quinagolide
surgery - VF compromise
failure of medical therapy
88
Describe prolactinomas in pregancy
pituitary gland gets bigger in pregnancy
dopamine agonists contraindicated
(prolactin) unhelpful
Cant do serial MRI in pregnancy
monitor visual fields if macroprolactinoma
89
Describe acromegaly
pituitary tumour secreting growth hormone
-post puberty - after birth plates fuse
pre puberty - gigantism
```
features - sweats and headaches
alteration of facial features
increased hand and feet size
visual impairment
cardiomyopathy
increased inter-dental space
```
90
How is acromegaly diagnosed?
glucose tolerance test
Glucose should suppress GH
measure IFG-1
long half life
more useful than random GH
Then MRI
91
Describe the treatment of acromegaly
first line - surgery - often tumour can't be fully removed
drugs - somatostatin analogue
octretide, before and after surgery
dopamine agonist
GH receptor agonist
radiotherapy - residual tumour / ongoing symptoms
92
Describe cushing's disease
pituitary tumour releasing ACTH
one of the causes of cushing syndrome
weight gain, thin skin, easy bruising, increased BP, osteoporosis
diagnosis- dexamethasone suppression testing
93
What is the treatment of cushing's disease
surgery first line
if surgery fails / inappropriate
bilateral adrenalectomy
medical therapy - ketoconazole / metyrapone
radiotherapy
94
Describe TSHoma
Pituitary tumour releasing TSH
rare
causing high TSH and high fT4
95
Describe diabetes insipidus
ADH deficiency - central or cranial
clinical feutres
polydipsia
polyuria
differential - nephrogenic diabetes insipidis
psychogenic polypisia
96
Describe central diabetes insipidus
```
Deficiency of ADH
idiopathic
trauma
pituitary tumour
pituitary surgery
pregnancy
familial
other
```
97
Describe the diagnosis of diabetes insipidus
try to stimulate its release
water deprivation test
assess ability to concentrate urine with ADH
98
Describe the treatment of diabetes insipidus
treat underlying cause
| DDACP - spray, tablet or injection
99
What are the functions of calcium?
```
muscle contraction
bone growth and remodelling
second messenger signalling
stabilisation of membranes
enzyme co-factor
secretion of hormones
```
100
What is ionised calcium regulated by?
parathyroid hormone and vitamin D
101
Describe the parathyroid glands
usually 4
posterior aspect of thyroid gland
10% are ectopic
supplied by inferior thyroid artery
102
What is the action of PTH in the kidneys?
reabsorption of calcium at distal tubule
internalises sodium-phosphate co-transporters at proximal tubule
inhibits Na+/H+ leading to bicarbonate wasting
103
What are the actions of PTH on the bones?
increased number and activity of osteoclasts in continuous PTH exposure
intermittent exposure increases anabolic activity of osteoblasts
104
Describe the actions of PTH in the gut
stimulates synthesis of active form of Vitamin D in kidney
| thereby increases calcium absorption from the gut
105
What do calcimimetic drugs do?
Target CaSR and inhibit PTH secretion
106
What does calcium sensing receptor do in the kidney?
increases urinary calcium and magnesium excretion
| increases sodium, potassium and chloride excretion
107
What does calcium sensing receptor do in the thyroid?
expressed in C cells
| stimulates calcitonin secretion
108
Describe vitamine D
steroid hormone
acts to increase serum calcium levels
precursors synthesised in the skin
active form is 1,25 dihydroxycholecalciferol
109
What are the actions of active vitamin D?
increases calcium and phosphate absorption from gut
bone mineralisation and mobilises calcium stores
immunomodulation
increases muscle strength
reduces insulin resistance
interacts with RAAS - role in prevention of CVD?
110
What are the symptoms of hypercalcaemia?
muscle weakness, bone pain, osteoporosis
confusion, depression, fatigue, coma
shortening of GTc, bradycardia, hypertension
anorexia, nausea, constipation, pancreatitism
polyuria, nephrogenic DI, stones, nephrocalcinosis
111
What are the PTH mediated causes of hypercalcaemia?
primary hyperparathyroidism
familial syndromes - MEN1 and MEN2
familial hypocalciuric hypercalcaemia
112
What are the PTH independent causes of hypercalcaemia?
```
malignancy
granulomatous disorders
vitamin D toxicity
Drugs - thiazides, lithium, calcium supplements
adrenal insufficiency
milk-alkali syndrome
immobilisation
```
113
What investigations can be carried out in hypercalcaemia?
```
history an exam
chest x-ray
FBC/ESR
TFTs
myeloma screen
synacthen test
Vit D
```
114
Describe malignancy and hypercalcaemia?
commonest cause of hypercalcaemia in hospitalised patients
solid organ tumours and haematological malignancies
causes hypercalcaemia through increased bone resorption and calcium release through 3 possible mechanisms
115
What are the 3 ways in which malignancy can lead to hypercalcaemia?
osteolytic metastases and myeloma
Tumour secretion of PTHrP - squamous cell lung cancer, oesophageal cancer, renal cell carcinoma, breast cancer
3 - tumour production of 1,25 dihydroxycholecaciferol
by activated macrophages - occurs in lymphoma
116
Describe vitamin D toxicity
increased bone resorption and gut absorption
ingestion of high does of calcitriol (Hyperparathyroid or renal disease)
resolves within 48 hours of stopping offending agent
117
Describe endogenous production of active vitamin D
lymphoma, sarcoid, wegeners
extra-renal activation of cholecalciferol
usually responsive to steroid treatment
118
Describe milk-alkali syndrome
hypercalcaemia, metabolic alkalosis, renal insufficiency
| due to ingestion of calcium and antacids
119
What are the general principles of managing hypercalcemia ?
stop offending / contributing medications
rehydration - saline - 3-4 litres over 24 hours is appropriate
loop diuretic?
bisphosphonates
steroids
120
What end organ damage can be caused by primary hyperparathyroidism?
bone - osteoporosis, other radiological changes - bone cysts, subperiosteal resorption
kidneys - renal calculi, nephrocalcinosis, renal impairment
other - pancreatitis
121
What are the investigations for primary hyperparathyroidism?
confirm diagnosis - drugs, UEs, PTH, urine calcium:creatine ratio
Vit D
end organ damage - DEXA, KUB/ renal US
other conditions - MEN1/2 if <40 or history of hyperparathyroidism in 1st degree relative
if surgery indication - localised abnormal gland
122
Describe Brown tumours
result of excess osteoclast activity
collection of osteoclasts, poorly mineralised bone and fibrous tissue
"brown" appearance because of haemosiderin deposition
123
What is the management of primary hyperparathyroidism?
parathyroidectomy - if causing problems
observation
medical treatment (only if not fit for surgery ) - bisphosphonates, cincacalcet - calcium sensing receptor antagonist - reduces serum (not urinary) calcium, doesn't prevent end organ damage
124
What are the complications of parathyroidectomy?
mechanical - vocal cord paresis
haematoma ceasing tracheal compression
metabolic - transient hypoglycaemia (suppression of remaining glands)
may require oral calcium / vitamin D supplementation
hungry bones - uncommon
occurs in patients who have significant bone disease pre-op or very elevated PTH
sudden withdrawal of PTH leads to imbalance between bone formation and resorption - marked net increase in uptake of calcium, phosphate and magnesium by bone
requires calcium and vitamin D supplementation
125
Describe vitamin D deficiency
```
poor sunlight exposure
malabsorption
gastrectomy
enzyme inducing drugs (anti-convulsants)
renal disease
```
126
Describe osteomalacia
classically associated with very low levels of vitamin S
failure to ossifiedy bones in adulthood as a result of vitamin D deficiency
hypo-mineralisation of trabecular and cortical bone
presents insidiously with bone pain, proximal myopathy, hypocalcaemia
low calcium, low phosphate, high alkaline phosphate, low vit D, elevated PTH
127
What is the treatment of vitamin D deficiency?
cholecalciferol -restore body stores and correct metabolic disturbance
```
alfacalcidol (active form)
in renal impairment
hypoparathyroidism
not measured by traditional lab vit D assay
higher risk of hypercalcaemia
```
128
Describe testosterone production
```
produced by leydig cells
steroid hormone
circulates bound to SHGB and albumin
free testosterone is active
activated to more potent form in target tissues
```
129
What are the effects of testosterone on growth?
```
sex organs
skeletal muscle
epiphyseal plates
larynx growth
secondary characteristics
```
130
What are other effects of testosterone ?
```
erythropoiesis
behaviour
muscle mass
mood
bone mass
libido
body shape
erectile function
spermatogenesis
```
131
What do sertoli cells do/?
form blood-testis barrier
remove damaged spermatocytes
secrete androgen binding protein
132
What are the clinical features of hypogonadism in children and young adults?
slow growth in teens
no pubertal growth spurt
small testes and phallus
lack of secondary development
133
What are the lineal features of hypogonadism in adults?
```
depression / low mood
poor libido
erectile problems
poor muscle bulk / power
poor energy
sparse body / facial hair
gynaecomastia
gyroid weight gain
great head hair
short phallus
small testes, abnormal consistency
```
134
Describe testing for gypogonadism
sex steroid deficiency?
testosterone - early morning, free testosterone, total , SHBG
LH and FSH
semen analysis
135
What are some causes of hypogonadotrophic hypogonadism?
```
pituitary tumour
pituitary surgery / Rx
head injury
genetic syndrome
cerebellar ataxia
Kallman's syndrome - isolated LH and FSH deficiency
```
136
Describe Kallman's syndrome
Commonest form of isolated gonadotrophin deficiency
failure of cell migration of GnRH cells to hypothalamus from olfactory node
associated with aplasia / hypoplasia of olfactory lobes - anosmia/hyposmia
also may be associated with deafness, renal agenesis, cleft lip
may have micropenins / crytochidism
137
Describe the genetics of Kallman's syndrome
Familial with variable penetration
| AD, AR and X-linked forms
138
Describe Kallman's syndrome in childhood
poor growth
| undescended testes
139
Describe Kallman's syndrome in adolescence
poor growth
small testes
micropenis
delayed / absent puberty features
140
Describe Kallman's syndrome in adults
slow, but adequate growth
small testes
small phallus
hypogonadal features
141
What are causes of primary gonadal disease?
```
chromosome defects - Kleinfelters
seminiferous tubule failure
adult leydig cell failure
crytochidsim
complex genetic syndromes - Myotonic dystrophy
```
142
Describe Klinefelter's syndrome
commonest genetic cause of male hypogonadism
XXY
clinically manifests at puberty
high LH and FSH but seminiferous tubules regress and leydig cells do not function normally
143
What are the clinical fescues of Klinefelter's?
delated puberty
suboptimal genital development
reduced secondary sexual characteristics
azospermia
behavioural issues / learning difficulties
androgen replacement +psychological support + fertility counselling
144
Describe hypogonadism treatment
androgen replacement therapy - oral, IM, topical
fertility treatment
hCH,
recombinant LH and FSH
GnRH pumps
145
What are the side effects of androgen replacement therapy?
```
mood issues
libido issues
increased haematocrit
possible prostate effects
acne, sweating
gynaecomastia
```
