Endocrinology Flashcards
1
Q
Disease by organ
pituitary and hypothalamus
A
- hyperprolactinaemia
- hypopituitarism
- pituitary tumours
2
Q
Disease by organ
parathyroid glands
A
hyperparathyroidism
hypoparathyroidism
3
Q
Disease by organ
breast
A
hyper prolactinaemia
4
Q
Disease by organ
Adrenals
A
addison’s disease
cushing’s syndrome
conn’s syndrome
phaeochromocytoma
5
Q
Disease by organ
Ovaries
A
PCOS
Menopause
Subfertility
6
Q
Disease by organ
Bone
A
Osteoporosis
Osteomalacia
7
Q
Disease by organ
Testes
A
Sub-fertility
Testicular failure
8
Q
Disease by organ
Kidneys
A
renin-dependent hypertension
9
Q
Disease by organ
Pancreas
A
Type 1 DM
Type 2 DM
10
Q
Disease by organ
Thyroid
A
Hyperthyroidism
hypothydroidism
Goitre
Carcinoma thyroid
11
Q
Hormones produced by the anterior pituitary
- stimulate peripheral glands and tissues
A
- GnRH (LHRH) (Gonadotrophin releasing hormone/ Lutenising hormone releasing hormone)
- GHRH (Growth hormone releasing hormone)
- Dopamine
- TRH (thyrotrophin-releasing hormone)
- CRH
(Somatostatin- depresses secretion of GHRH, dopamine, TRH)
12
Q
Hormones secreted by the posterior pituitary
- storage organ
A
Vasopressin (renal tubules)
Oxytocin (breasts/uterus)
(produced in supraoptic and paraventricular nuclei of hypothalamus
13
Q
GnRH pathway
A
GnRH (LHRH) (anterior pituitary)
–> LH + FSH
–> Ovaries + testes
–> Androgen/ Sperm, Oestrogens/Ovaries
14
Q
GHRH pathway
A
Secreted by anterior pituitary
–> GH
-> Liver
–> Growth (via IGF)
suppressed by somatostatin
15
Q
Dopamine pathway
A
Secreted by anterior pituitary
–> Prolactin
–> Breasts/Gonads
–> Lactation
suppressed by somatostatin
16
Q
TRH Pathway
A
secreted by anterior pituitary
–> TSH
–> Thyroid
–> Thryoxine
Suppressed by somatostatin
17
Q
CRH pathway
A
Secreted by anterior pituitary
–> ACTH
–> Adrenals
–> Steroids
18
Q
Pituitary space occupying lesions and tumours
A
most commonly benign adenomas
symptoms arise from inadequate hormone production, excess hormone secretion or from local tumour effects
19
Q
Under production in pituitary SOL
A
disease at hypothalamic or putuitary level
results in clinical features of hypopituitarism
20
Q
Overproduction in pituitary SOL
A
- Growth Hormone excess –> acromegaly in adults/ gigantism in children
- prolactin excess - causing galactorrhoea or clinically silent
- excess ACTH secretion - Cushing’s disease or Nelson’s syndrome
21
Q
Local effects in pituitary SOL
A
- optic chiasm –> bitemporal hemianopia
- cavernous sinus with III, IV and VI cranial nerve lesions
- bony structures and the meninges causing headache
- hypothalamic structures - obesity, altered appetite and thirst, precocious puberty
- ventricles- interruption of CSF flow and hydrocephalus
22
Q
Hypopituitarism
A
Multiple deficiences = tumour growth or destructive lesion
- progressive loss of function with GH and gonadotrophins being affected first and TSH & ACTH last
- hyperprolactinaemia occurs early becuase of loss of tonic inhibitory control by dopamine
- pan hypopituitarism is a deficiency of all anterior pituitary hormones
- vassopressin and oxytocin secretion is only affected if the hypothalamus is involoved
23
Q
Aeitology of Hypopituitarism
A
Neoplastic - primary/secondary/lymphoma
Infective - basal meningitis (TB)/encephalitis/syphilis
Vascular - pituitary apoplexy/ Sheehan’s syndrome/ carotid artery aneurysm
Immunological - pituitary antibodies
Congenital - kallmann’s syndrome
Traumatic- skull fracture/ surgery
Infiltrations- sarcoidosis/haemochromatosis
Others- radiation/chemo/empty sella syndrome
Functional - anorexia/ starvation/ emotional deprivation
24
Q
Clinical features of hypopituitarism
A
Gonadotrophin deficiency - loss of libido/amenorrhea/ erectile dysfunction
Hyperprolactinaemia - galactorhhoea & hypogonadism
GH deficiency - short strature, clinically silent in adults
Secondary hypothyroidism & adrenal failure –> tiredness, slowness of thought and action, mild hypotension
long standing hypopituitarism - hairlessness
25
Congenital deficiency of gonadotrophin-releasing hormone
(GnRH)
Kallmann's syndrome
- anosmia
- colour blindness
- cleft palate
- renal abnormalities
- male hypogonadism
26
Sheehan's syndrome
pituitary infarction following severe post partum haemorrhage
27
pituitary apoplexy
rapid enlargement of a pituitary tumour due to infarction of haemorrhage
- severe headache and sudden severe visual loss
- sometimes followed by acute life threatening hypopituitarism
28
Empty sella syndrome
sella turcia (bony shell around pituitary
appears empty on imaging
pituitary may be placed eccentrically - function normal
or
pituitary atrophy - after injury/ surgery/radiotherapy
and associated hypopituitarism
29
INvestigating hypopituitarism
- each axis
- normal gonadal function suggests multiple defects of anterior pituitary is unlikely
- measure basal hormone levels and stiumlatory test
30
Management of hypopituitarism
- steroid and thyroid hormones are essential
- androgens and oestrogens are replaced for symptomatic control
- LH & FSH given if fertility is desirable
- GH given to growing children
31
Warnings in management of hypopituitarism
- thyroid replacement should not commence until normal gluccorticoid function has been demonstrated/ replacement steroids have started --> otherwise may cause adrenal crisis
- glucocorticoid deficiency masks impaired urine concentrating ability
- diabetes insipidus is apparent after steroid replacement
32
Pituitary hypersecretion syndromes
pituitary growth hormone
- secreted in a pulsatile fashion- also stimulated by Ghrelin (Secreted by the stomach)
- acts indirectly by inducing insulin-like growth factor (liver)
33
CLinical features of pituitary growth hormone
acromegaly/ gigantism
- tumour expansion- headache/visual field loss/ hypopituitarism
- changes in physical features and appearance - compare to old pictures- growth of liver, muscle, bone or fat
34
INvestigations in pituitary hypersecretion syndromes
- plasma GH
- serum IGF-1
- Glucose tolerance test- if positive failure of normal suppression of serum GH
- MRI
- plot visual field defects
- serum prolactin
35
Symptoms of acromegaly
changes in appearance
- increased size of hands/feet
- headaches/ visual field changes/
- excessive sweating
- tiredness
- weight gain
- amenorrhoea/oligomenorrhea
- galactorrhoea
- impotence/ loss of libido
- goitre
- deep voice
- breathlessness
- pain/tingling in hands
- polyuria/ polydipsia
- muscular weakness
- joint pain
36
Signs of acromegaly
- prominent supraorbital ridge
- prognathism
- interdental separation
- macroglossitis
- hirsuitism
- thick greasy skin
- spade like hands or feet- tight rings
- carpal tunnel syndrome
- visual field defects
- galactorrhoea
- hypertension
- oedema
- heart failure
- arthropathy
- proxmial myopathy
- glycosuria
37
Management of acromegaly
reduce serum IGF-1
- transsphenoidal surgical resection - complications = hypopituitarism, diabetes insipidius, CSF rhinorrhoea and infection)
- medical therapy when surgery has failed
- - somatostatin analogues - pcterotide and lanreotide
- - dopamine agonists - bromocriptine or cabergoline
- pegvisomant
- external radiotherapy
38
Hyper prolactinaemia
normally under tonic inhibition by dopamine from the hypothalamus
- physiological increase in serum prolactin during pregnancy, lactation and severe stress
39
Aetiology of prolactinaemia
- prolactinoma
- pituitary/hypothalamic tymours (interfering with dopamine inhibition of prolactin release)
- primary hypothroidism (high TRH stimulate prolactin)
- drugs - metoclopramide, phenothiazides, oestrogens, cimetidine,
- PCOS
- acromegaly
40
Clincial features of hyperprolactinaemia
- galactorrhoea
- oligo or a mennorrhoea
- decreased libido, subfertility or erectile dysfunction
- if pituitary tumour- headache and visual field defects
41
investigations of hyperprolactinaemia
- serum prolactin level (at least 3)
- thyroid function tests
- MRI of pituitary
- pituitary function tests and visual fields
42
Management of hyperprolactinaemia
- withdraw any drugs that could be causing (metoclopramide, phenothiazides, oestrogens, cimetidine)
- dopamine agonist - cabergoline/ bromocriptine
43
Hypothyroidism
primary from thyroid gland disease
| secondary to hypothalamic or pituitary disease
44
Aetiology of hypothyroidism
- more common in women
- incidence increases with age
- most commonly autotimmune thryoiditis in places with enough iodine
- iatrogenic
- drug induced
- iodine deficiency
- congential hypothyroidism
45
Thyroid function tests in thyrotoxicosis
- low TSH
- high free T4
- high free T 3
46
Thyroid function tests in primary hypothyroidism
- high TSH
- low or low-normal free T4
- low or normal free T3
47
Thyroid function tests in TSH deficiency
- low or low-normal TSH
- low or low-normal free t4
- low or normal free T3
48
Thyroid function tests in T3 toxicosis
- low TSH
- normal free T4
- high free T3
49
Thyroid function tests in borderline hypothyroidism
- slightly elevated TSH
- normal free T4
- normal free T3
50
Autoimmune thyroiditis
- may be associated with goitre (Hashimoto;s) or thryoid atrophy
- cell and anti-body mediated destruction of thyroid tissue
- serum antibodies to thyroglobulin, thyroid peroxidase enzyme (thyroid microsomal antibodies) and anti-bodies that block binding to TSH receptors
- associated with other autoimmune conditions. can be transient post-partum = hypo-hyperthyroidism
51
Iatrogenic hypothyroidism
thyroidectomy
radioactive iodenine treatment
external neck irradiation for head and neck cancer
52
Drug induced hypothyroidism
carbimazole
lithium
amiodarone
interferon
53
Iodine deficiency hypothyroidism
particularly moutainous regions - alps, himalayas, south america
- goitre is common
- iodine excess can also cause hypothyroidism in patients with pre-existing thyroid disease
54
Congenital hypothyroidism
thyroid aplasia
thyroid dysplasia
defective synthesis of thryoid hormones
55
Symptoms of hypothyroidism
```
Tiredness/ malaise
weight gain
anorexia
cold intolerance
poor memory
change in appearance
depression
poor libido
goitre
puffy eyes
dry/brittle/unmanageable hair
dry/coarse skin
arthralgia
myalgia
muscle weakness/stiffness
constipation
menorrhagia/oligomenorrhoea
psychosis
coma
deafness
```
56
Signs of hypothyroidism
```
BRADYCARDIC
B= bradycardia
R= reflexes relax slowly
A= ataxia
D= dry, thin hair/skin
Y= yawning/drowsy/coma
C= cold hands ± low temp
A= ascite ± non-pitting oedema ± pericardial/pulmonary effusion
R= round puffy face/double chin/obese
D = defeated demeanour
I = Immobile ± ileus
C = CCF
```
57
Diagnosis of hypothyroid
Low free T4 and low TSH
raised cholesterol and triglyceride
macrocytosis
normocytic anaemia
58
Associations with hypothyroidism
```
Other autoimmune diseases
Turner's & Down's syndrome
Cystic fibrosis
primary biliary cirrhosis
ovarian hyperstimulation
POEMS - polyneuropathy, organomegaly, endocrinopathy, m-protein band + skin tethering/pigmentation
```
59
Pregnancy problems with hypothyroidism
```
Eclampsia
anaemia
prematurity
low birth weight
still birth
PPH
```
60
Treatment of hypothyroidism
Young and healthy
Levothryoxine 50-100 micrograms w/ regular reviews
| once normal review annually
61
Treatment of hypothyroidism
elderly/ ischaemic heart disease
start with 25 micrograms/24hrs
| increase dose by 25 micrograms / 4 weeks according to TSH
62
Amiodarone and hypothyroidism
iodine rich drug
2% of will get significant thryoid problems from it
--> thyroxicosis
thyroidectomy may be necessary if amiodarone cannot be discontinued
half life of amiodarone is 80 days so symptoms may continue after withdrawal
63
Subclinical hypothryoidism
low TSH with normal T4 &T3
- low threshold for treatment (if THS >10, +ve thyroid autoantibodies, past Graves or other organ specific autoimmunity)
- risks from well-monitored treatment of subclincial hypothyroidism are small but increased risk of AF and osteoporosis
64
Subclincial hyperthyroidism
low TSH with T4 and T3
41% increase in mortality from all causes vs euthyroid
- confirm suppressed TSH
- check for non-thryoidal cause
-treat on an individual basis
- carbimazole or propylthiouracil or radioiodine
65
Parathyroid hormone
secreted in response to low ionised Ca2+ levels
controlled by negative feedback via Ca2+
Increases osteoclast activity - releasing calcium and phosphate from the bones
increases calcium and reduces phosphate reabsorption in the kidney
active 1,25 vit D3 production increased
overall - increases calcium and decreases phosphate
66
Causes of primary hyperparathryoidism
```
solitary adenoma (80%)
hyperplasia of all glands (2-%)
parathyroid cancer (<0.5%)
```
67
Presentation of Hyperparathyroidism
raised Ca2+ on routine tests
1. weak, tired, depressed, thirsty, dehydrated byt polyuric, renal stones, abdo pain, pancreatitis and ulcers
2. Bone resorption effects - pain, fractures, osteoporosis/osteopenia
3. raised BP
68
Hyperparathyroidism
Investigations
```
raised Ca2+ and PTH
low phosphate
raised alk phos
24 urinary Ca2+ elevated
ostetitis fibrosa cystica on imaging - subperiosteal erosions, cysts or brown tumours of phalanges ± acrosteolysis ± pepper pot skull
```
69
Treatment of hyperparathyroidism
- mild - increase fluid intake
- avoid thiazides and high Ca2+ and vit D intake
- excision of adenoma or all 4 hyperplastic glands - prevents fractures and peptic ulcers
70
Complications of hyperparathyroidism treatments
hypoparathyroidism
recurrent laryngeal nerve damage - hoarse voice
symptomatic low calcium - hungry bone syndrome (check Ca2+ daily for 14/7 post op)
71
Indications to treat hyperparathyroidism
high serum/urine calcium,
bone disease, osteoporosis,
renal caliculi,
low renal function
72
Secondary hyperparathryoidism
low Ca2+, appropriately elevated PTH
causes - low vit D intake, chronic renal failure
Rx- correct causes, phosphate binders, vit D, cinacelet
73
tertiary hyperparathyroidism
elevated Ca2+, very elevated PTH (inappropriate)
occurs after significantly prolonged secondary hyperparathyroidism
glands act autonomously - hyperplastic or adenomatous changes
Ca2+ increases from elevated secretion of PTH unlimited by feedback control
Seen in chronic renal failure
74
Malignant hyperparathyroidism
parathyroid related protein (PTHrP) produced by some squamous cell lung cancers, breast and renal cell carcinomas
mimics PTH causes Ca2+ to rise
PTH is low- PTHrP not detected on normal assay
75
Primary hypoparathyroidism
low PTH secretion due to gland failure
low Ca2+, high or normal phosphate, normal alk phos
Signs of hypocalcaemia ± autoimmune comorbidities
Causes- autoimmune, confenital
treat with calcium supplements + calcitriol or synthetic PTH
76
Secondary hypoparathyroidism
radiation, surgery hypomagnesaemia
77
psuedohypoparathyroidism
failure of target cell response to PTH
Signs- short metacarpals, round face, short stature, calcified basal ganglia, low IQ
low Ca2+, raised PTH, normal alk phos,
78
psuedopsuedohypoparathyroidism
morpholoical features of pseudohypoparathyroidism
normal biochem
cause is genetic
79
MEN
multiple endocrine neoplasia
Functioning hormone producing tumours in multiple organs
MEN-1 = neurofibromatosis, Von Hippel-Lindau and peutz-jeghers syndrome, carney complex and endocrine tumours
MEN-1 is a tumour suppressing gene- menin alters transcription activation. presents 3rd-5th decade
MEN-2 associated with ret - receptor tyrosine kinase
80
Adrenal cortex
Physiology
1. Glucocorticoids (cortisol) affect carbohydrate, lipid and protein metabolism
2. Mineralocorticoids - control sodium and potassium balance (aldosterone)
3. Androgens - sex hormones
corticotropin releasing factor from hypothalamus --> stimulates ACTH from pituitary--> cortisol and androgens from adrenal cortex
81
Cushings syndrome
clinical state produced by chronic glucocorticoid excess + loss of normal feedback mechanisms of hypothalamo-pituitary-adrenal axis
loss of circadian rhythm of cortisol secretion
chief cause - oral steroids
endogenous causes - 80% due to elevated ACTH usually caused by a pituitary adenoma (Cushing's disease)
82
ACTH dependent causes of Cushing's Syndrome
Cushing's disease
bilateral adrenal hyperplasia from an ACTH secreting pituitary adenoma (usually microadenoma)
30-50yrs
low dose dexamethasone test leads to no change in plasma cortisol
83
ACTH dependent causes of Cushing's Syndrome
Cushing's disease
Tests
1st - Overnight dexamethasone suppression test 1mg overnight, 8am cortisol- normally would be half (24hr urinary free cortisol is the alternative)
2nd - 48hr dexamethasone suppression/ high dose 48hr dexamethasone suppression test/ midnight cortisol
84
ACTH dependent causes of Cushing's Syndrome
Ectopic ACTH production
small cell lung cancer
carcinoid tumours
pigmentation, hypokalaemic metabolic acidosis (high cortisol --> mineralocorticoid activity), weight loss, hyperglycaemia
classical features of cushing's are normally absent
even high dose Dexamethasone (8mg) fails to suppress cortisol production
85
ACTH dependent causes of Cushing's Syndrome
Rarely ectopic CRF production
some thyroid (medullary) and prostate cancers
corticotrophin releasing hormone
86
ACTH independent causes of Cushing's Syndrome
- low ACTH due to -ve feedback
- adrenal adencoma/cancer
- adrenal nodular hyperplasia
- iatrogenic - pharmacological doses of steroids
- rarely - Carney complex, McCune-Albright syndrome
87
Symptoms of Cushing's
- increasing weight
- mood change- lethargy, depression, irritablility, psychosis
- proximal weakness
- gonadal dysfunction- irregular periods, hirsuitism, ED
- acne
- recurrent Achilles tendon rupture
- occasional virilisation if female
88
Signs of Cushing's
- central obesity
- plethoric (full of fluid)
- moon face
- buffalo neck hump
- supraclavicular fat distribution
- skin and muscle atrophy
- bruises
- purple abdominal striae
- osteoporosis
- high BP
- high glucose
- infection prone
- poor healing
89
Cushing's Treatments
- iatrogenic -> stop medicines if possible
- cushing's disease -> remove pituitary adenoma or bilateral adrenalectomy if source unlocatable or recurrence
- adrenal adenoma or carcinoma - adrenalectomy - cures adenomas but rarely cures cancer. Radiotherapy & adrenolytic drugs (mitotane)
- ectopic ACTH - surgery if tumour located 1
90
Prognosis of Cushing's
Untreated- high vascular mortality
treated - good prognosis, but myopathy, obesity, menstrual irregularity, high BP, osteoporosis, subtle mood changes and DM often remain
91
Adrenal insufficiency
adrenal insufficiency
- exogenous steroid suppression of pituitary adrenal axis
- overwhelming sepsis
- metastatic cancer
- addison's disease
92
Primary adrenocortical insufficiency
Addison's disease
rare but may be fatal
- destruction of adrenal cortex leads to glucocorticoid (cortisol) and mineralocorticoid (aldosterone) deficiency
- signs are capricious
93
Causes of adrenal insufficiency
```
Autoimmunit
TB
adrenal metastases
lymphoma
opportunistic infections in HIV (CMV, mycobacterium avium)
adrenal haemorrhage
congenital
```
94
SYmptoms of adrenal insufficiency
- lean
- tanned
- tired
- tearful ± weakness
- anorexia
- dizzy
- faints
- flu- like myalgia/arthralgias
Mood- depression, psychosis, low-self esteem
GI - N&V, abdominal pain, diarrhoea/constipation
Pigmented palmar creases and buccal mucosa
postural hypotension
vitiligo
95
Signs of critical deterioration in adrenal insufficiency
Shock ( high pulse, vasoconstriction, postural hypotension, oliguria, weak, confused, comatose
- manage with IV glucose, IV fluids, correct electrolytes, IV/IM hydrocortisone,
96
Tests for adrenal insufficiency
```
low sodium, high potassium
low glucose
uraemia, high calcium, eosinophilia, anaemia
Synacthen (short ACTH stimulation)
plasma renin and aldosterone
```
97
Treatment of adrenal insufficiency
replace steroids ~15-25mg/day in 2-3 doses
mineralocorticoids to correct postural hypotension
tell drs/dentists/surgeons of steroid use
add extra hydrocortisode before strenuous exercise, double in febrile illness, injury or stress
98
Secondary adrenal insufficiency
most commonly iatrogenic from long term steroids
99
Primary hyperaldosteronism
excess production of aldosterone
independent of the renin-angiotensin system causing increases in sodium and water retention
low renin release
- hypertension, hypokalaemia or alkalosis in someone not on diuretics
100
Symptoms of hyperaldosteronism
asymptomatic
signs of hypokalaemia (muscle weakness, hypotonia, hyporeflexia, cramps, tetany, palpitations, light-headedness (arrhythmias), constipation)
parasthesia, polyuria, polydipsia, high BP
101
Causes of hyperaldosteronism
2/3 solitary aldosterone producing adenoma
(Conn's syndrome)
1/3 bilateral adrenocortical hyperplasia
Rarely- adrenal carcinoma, glucocortioid-remedial aldosteronism
102
Tests for hyperaldosteronism
U&E, renin and aldosterone
103
Treatment of hyperaldosteronism
Conn's --> Laproscopic adrenalectomy
spironolactone
Hyperplasia - spironalactone, amiloride oR eplernone
Glucocorticoid-remedial aldosteronism - dexamethasone
Adrenal carcinoma - surgery ± post-operative adrenolytic therapy (mitotane)
104
Secondary hyperaldosteronism
high renin from reduced renal perfusion e.g. renal artery stenosis, accelerated hypertension, diuretics, CCF or hepatic failure
105
Bartter's syndrome
congenital salt wasting - sodium/chloride leak in the loop of Henle
failure to thrive, polyuria and polydipsia
BP normal
sodium loss leads to volume depletion, increases renin and aldosterone production
--> hypokalaemia, metabolic acidosis, high urinary potassium and chloride
Rx- K+ replacment, NSAIDs and ACE-i
106
Phaeochromocytoma
Rare catecholamine producing tumours
arise from sympathetic paraganglia
usually found in the adrenal medulla
episodic headache, sweating, tachycardia
Raised WCC, plasma and urinary metadrenaline and normetadrenaline ±clonidine suppression test
Rx- surgery w/ alpha blockade pre-op
107
Hyperaldosteronism
solitary aldosterone-producing adenoma Conn's syndrome
tumour in the zona Glomerulosa, zona Fasiculata or zona Reticularis with syndromes of raised MINERalocorticoids, Glucocorticoids, Androgens respectively
GFR= miner GA
108
Gynaecomastia
abnormal breast tissue in men
may occur in normal puberty
oestrogen/androgen ratio raised
Causes- hypogonadism, liver cirrhosis, hyperthyroidism, tumours, drugs (oestrogens, spironolactone, digoxin, testosterone, marijuana)
109
Erectile Dysfunction causes
Psychological
Big 3: smoking, alcohol, diabetes
endocrine: hypogonadism, hyperthyroidism, raised prolactin
cord lesions, MS< autonomic neuropathy,
pelvic surgery, radiotherapy, artheroma, renal or hepatic failure, prostatic hyperplasia, penile anaomalies, drugs (digoxin, beta-blockers, diuretics, antipsychotics, antidepressants, oestrogens, finasteride, narcotics)
110
Male hypogonadism
failure of testes to produce testosterone, sperm or both
small testes, low libido, erectile dysfunction, loss of pubic hair, loss of muscle bulk, increased fat, gynaecomastia, osteoporosis low mood
if pre-pubescet - decreased virilisation, incomplete puberty, eunuchoid body, reduced secondary sex characterists
111
Causes of primary hypogonadism (male)
testicular failure
- local trauma, torsion, chemotherapy/irradiation
- post-orchitis e.g. mumps, HIV, brucellosis, leprosy
- renal failure, liver cirrhosis or alcohol excess
- Chromosomal abnormalities
112
Causes of secondary hypogonadism (male)
low gonadotrophins from
- hypopituitarism
- prolactinoma
- Kallmann's syndrome - isolated gonadotrophin releasing hormone deficiency
- systemic illness
- Laurence-Moon-Biedl and PRader Willi syndromes
- Age
113
Diabetes insipidus
passage of large volumes (3L+/day) of dilute urine
due to impaired water resorption from the kidney
reduced ADH secretion from posterior pituitary (cranial)
impaired response of kindey to ADH (nephrogenic)
114
Symptoms of diabetes insipidus
polyuria
polydipsia
dehydration
symptoms of hypernatraemia (lethargy, thirst, weakness, irritability, confusion, coma)
115
Causes of cranial diabetes insipidus
```
idiopathic
congenital
tumour- craniopharyngioma, metastases, pituitary tumour
trauma
hypophysectomy
autoimmune hypophysitis
infiltration - histiocytosis/ sarcoidosis
vascular- haemorrhage
infection - meningioencephalitis
```
116
Causes of nephrogenic diabetes insipidus
- inherited
- metabolic - low potassium, high calcium
- drugs - lithium, demeclocycline
- chronic renal disease
- post- obstructive uropathy
117
Tests for diabetes insipidus
```
U&E
glucose (exclude DM)
calcium
serum and urinen osmolalities
water deprivation test
```
118
SIADH
| syndrome of inappropriate ADH secretion
important but over diagnosed cause of hyponatraemia
concentrated urine in the presence of hyponatraemia and low plasma osmolality in the abscence of hypovolaemia, oedema or diuretics
119
Causes of SIADH
Malignancy - small cell lung, pancreas, prostate, thymus or lymphoma
CNS - meningoencephalitis, abscess, stroke, SAH/SDH, head injury, neurosurgery, Guillan-Barre, vasculitis or SLE
Resp- TB, pneumonia, abscess, aspergillosis
Endo- hypothyroidism
Drugs - opiates, psychotropics, SSRIs or cytotoxics
Other - acute intermittent porphyria, trauma, major abdominal/ thoracic surgery, symptomatic HIV
120
Treatment of SIADH
treat cause
fluid restriction
consider salt ± loop diuretics if severe
121
Symptoms of hyperthyroidism (thyrotoxicosis)
```
diarrhoea
weight loss
appeitie increase
overactive
sweats
heat intolerance
palpitations
tremor
irritability
labile emotions
oligomenorrhoea ± infertility
```
Rarely: psychosis, chorea, panic, itch, alopecia, urticaria
122
Signs of hyperthyroidism (thyrotoxicosis)
```
pulse - fast/ irregular
warm, moist skin
fine tremor
palmar erythema
thin hair
lid lag/retraction
goitre
```
thyroid nodules or bruit
123
Signs of Graves Disease
1. Eye disease - exopthalmos, ophthalmoplegia,
2. Pre-tibial myxoedema - oedematous swelling above lateral malleoli
3. thyroid acropachy - extreme manifestation with clubbing painful finger and toe swelling and periosteal reaction in limb bones
124
Tests in thyrotoxicosis
```
suppressed (low) TSH
elevated T4 and T3
mild normocytic anaemia, mild neutropenia (Graves)
raised ESR, calcium, LFTs
Check thyroid autoantibodies
```
125
Graves disease
2/3 of hyperthyroidism
circulating IgG autoantibodies binding to and activating G-protein coupled thyrotropin receptors
causes smooth thyroid enlargement and increased hormone production (esp T3) and reaction with orbital autoantigens
- triggers: stress, infection, childbirth
associated with other autoimmune disease
126
Toxic multinodular goitre
seen in elderly and iodine deficient areas
nodules that secrete thyroid hormones
surgery indicated for compressive symptoms from enlarged thyroid (dysphagia or dyspnoea)
127
toxic adenoma
hyperthyroidism
solitary nodule producing T3 and T4
| nodule 'hot' on isotope scan, rest of the gland is suppressed
128
Ectopic thyroid tissue
hyperthyroidism
metastatic follicular thyroid cancer or struma ovarii
| ovarian teratoma with thyroid tissue
129
Exogenous causes of hyperthyroidism
iodine excess - food contamination , contrast media
| levothyroxine
130
Other causes of hyperthyroidism
1. Sub acute de Quervain's thryoiditis
2. Drugs - amiodarone, lithium
3. Post-partum
4. TB (rare)
131
Treatment of hyperthyroidism
1. Drugs -->beta blockers and anti-thyroid medication - carbimazole (titration or block and replace)
2. Radioiodine
3. Thyroidectomy
132
Complications of hyperthyroidism
```
heart failure (thyrotoxic cardiomyopathy)
angina
AF
osteoporosis
ophthalmopathy
gynaecomastia
```
133
Thyroid eye disease
symptoms
```
eye discomfort
grittiness
increased tear production
photophobia
diplopia decreased acuity
afferent pupillary defect
```
134
Thyroid eye disease
signs
```
exophthalmos
proptosis
conjunctival oedeam
corneal ulceration
papilloedema
loss of colour vision
ophthalmoplegia
```
135
Signs and symptoms of thyrotoxic storm (hyperthyroid crisis)
```
severe hyperthyroidism
high temp
agitation
confusion
coma
tachycardia
AF
D&V
goitre
thyroid bruit
acute abdomen
heart failure
cardiovascular collapse
```
136
Precipitants of hyperthyroid crisis
```
recent thyroid surgery
radioiodine
infection
MI
trauma
```
137
Treatment of hyperthyroid crisis
Grand strategy
1. Counteract peripheral effects of thyroid hormones
2. Inhibit thyroid hormone synthesis
3. Treat systemic complications
138
Step by step management of hyperthyroid crisis
```
IV access, fluids, NG tube if vomiting
take blood
sedate if necessary
propanolol/ ultra-short acting B-Blockers/ diltiazem
High dose digoxin
antithyroid drugs - carbimazole
hydrocortisone/IV dexamthasone
co-amox if suspected infection
```
139
PCOS
most common hormonal disorder affecting women
multiple small cysts within the ovary - arrested follicular development
excess androgen production from the ovaries (and adrenals)
associated with hyperinsulinaemia, insulin resistance, T@DM, HTN, hyperlipidaemia and increased CVD
140
Clinical features of PCOS
amenorrhoea/ oligomenorhoea
hirsuitism
acne
usually beginning shortly after menarche
associated with obesity
mild virilisation (clitoromegaly, recent onset frontal balding, deepening of voice and loss of female body shape) in severe cases
141
Criteria for PCOS diagnosis
- menstrual irregularity
- clinical or biochemical evidence of hyperandrogenism
- Polycystic ovaries on USS
142
Investigations of PCOS
- sex hormones- raised free androgen index, total testosterone raised
- serum prolactin slightly elevated in PCOS
- serum 17-hydroxyprogesterone elevated in non-classice adrenal hyperplasia
143
Management of PCOS
- local therapy for hirsuitism - waxing/ bleaching etc
- systemic - oestrogens, cyproterone acetate, spironolactone, finasteride
- cyclical oestroen/ progesterone
- treat infertility - anti-oestrogen clomifene for induction of ovulation
144
Hypothalamic causes of amenorrhoea
GnRH deficiency - Kallmann's syndrome or isolated
weight loss, physical exercise, stress
post oral contraceptive therapy
145
Pituitary causes of amenorrhoea
hyperprolactinaemia
| hypopituitarism
146
Gonadal causes of amenorrhoea
PCOS
premature ovarian failure - autoimmune basis
defective ovarian development (dysgenesis)
androgen-secreting ovarian tumours
radiotherapy
147
Other diseases causing amenorrhoea
thyroid dysfunction
Cushing's syndrome
adrenal tumours
severe illness
148
Uterine/ vaginal abnormalities causing amenorrhoea
imperforate hymen
| absent uterus
149
Investigating amenorrhoea
- basal serum FSH/LH, oestrogren and prolactin
- USS ovaries
- laproscopy and ovarian biopsy
- pituitary MRI
- serum testosterone
150
Management of amenorrhoea
treat cause
cyclical oestrogens
human LH/FSH in isolated GnRH deficiency or hypopituitarism
