Endocrine Flashcards
1
Q
myxoedema coma treatemnt
A
thyroxine and hydrocortisone
2
Q
hypothyroidism features
A
General
Weight gain
Lethargy
Cold intolerance
Skin
Dry (anhydrosis), cold, yellowish skin
Non-pitting oedema (e.g. hands, face)
Dry, coarse scalp hair, loss of lateral aspect of eyebrows
Gastrointestinal
Constipation
Gynaecological
Menorrhagia
Neurological
Decreased deep tendon reflexes
Carpal tunnel syndrome
A hoarse voice is also occasionally noted.
3
Q
SGLT-2 inhibitor mechanism
A
reversibly inhibit sodium-glucose co-transporter 2 (SGLT-2) in the renal proximal convoluted tubule to reduce glucose reabsorption and increase urinary glucose excretion.
4
Q
side effects SGLT-2 inhibitors
A
urinary and genital infection (secondary to glycosuria). Fournier’s gangrene has also been reported
normoglycaemic ketoacidosis
increased risk of lower-limb amputation: feet should be closely monitored
Patients taking SGLT-2 drugs often lose weight, which can be beneficial in type 2 diabetes mellitus.
-agliflozin
5
Q
mild hyponatraemia management
A
130-134 mmol/l
Non-specific symptoms such headache, lethargy, nausea, vomiting, dizziness, confusion, and muscle cramps
Fluid restriction (less than 800 mL/day) Loop diuretics
6
Q
moderate hyponatraemia Mx
A
20-129 mmol/l
Hypertonic saline in first 3-4 hours to increase Na+ >120 mmol/l
Rest is the same as mild
7
Q
severe hyponatraemia Mx
A
Less than 120 mmol/l
Seizures, coma, and respiratory arrest
Bolus of hypertonic saline until symptom resolution
With or without conivaptan
8
Q
what is conivaptan?
A
Vasopressin/ADH receptor antagonists (conivaptan):
These act on V1 and V2 receptors. The V1 receptors cause vasoconstriction while the V2 receptors results in selective water diuresis, sparing the electrolytes.
They should be avoided in patients who have hypovolemic hyponatremia.
Vasopression/ADH receptor antagonists can stimulate the thirst receptors leading to the desire to drink free water. They can be hepatotoxic in patients with underlying liver disease.
9
Q
hyponatraemia Mx complications
A
Osmotic demyelination syndrome (central pontine myelinolysis)
can occur due to over-correction of severe hyponatremia
to avoid this, Na+ levels are only raised by 4 to 6 mmol/l in a 24-hour period
symptoms usually occur after 2 days and are usually irreversible: dysarthria, dysphagia, paraparesis or quadriparesis, seizures, confusion, and coma
patients are awake but are unable to move or verbally communicate, also called ‘Locked-in syndrome’
10
Q
causes of hypertonic hyponatraemia
A
hyperglycaemia
mannitol
11
Q
causes of isotonic hyponatraemia
A
hyperproteinaemia
hyperlipidaemia
12
Q
hypotonic hyponatraemia need to look at…
A
fluid status
13
Q
Low serum osmolality with dehydration
A
suggests salt and water loss from the kidneys or elsewhere. Low urinary sodium (<20 mEq/L) in these patients is suggestive of GI or sequestrational loss, such as due to vomiting, diarrhoea or third spacing. Normal urinary sodium (>20 mEq/L) is suggestive of renal loss, such as due to diuretics, mineralocorticoid deficiency, renal tubular acidosis, cerebral salt wasting or salt wasting nephropathy.
14
Q
Low serum osmolality with euvolaemia
A
suggestive of redistribution. Urine osmolality <100 mOsm/kg may be due to primary polydipsia or beer potomania syndrome; urine osmolality >100mOsm/kg suggest SIADH, hypothyroidism or glucocorticoid deficiency.
15
Q
Low serum osmolality with hypervolaemia
A
suggestive of water retention. Low urinary sodium (<20 mEq/L) in this case is suggestive of renal failure as a cause, while normal urinary sodium (>20 mEq/L) suggests other causes of fluid overload such as heart failure, liver cirrhosis, nephrotic syndrome or hypoalbuminaemia.
16
Q
SIADH causes
A
Malignancy
small cell lung cancer
also: pancreas, prostate
Neurological stroke subarachnoid haemorrhage subdural haemorrhage meningitis/encephalitis/abscess
Infections
tuberculosis
pneumonia
Drugs sulfonylureas* SSRIs, tricyclics carbamazepine vincristine cyclophosphamide
Other causes
positive end-expiratory pressure (PEEP)
porphyrias
17
Q
SIADH Mx
A
correction must be done slowly to avoid precipitating central pontine myelinolysis
fluid restriction
demeclocycline: reduces the responsiveness of the collecting tubule cells to ADH
ADH (vasopressin) receptor antagonists have been developed
18
Q
gynaecomastia causes
A
physiological: normal in puberty syndromes with androgen deficiency: Kallman's, Klinefelter's testicular failure: e.g. mumps liver disease testicular cancer e.g. seminoma secreting hCG ectopic tumour secretion hyperthyroidism haemodialysis drugs: see below
Drug causes of gynaecomastia spironolactone (most common drug cause) cimetidine digoxin cannabis finasteride GnRH agonists e.g. goserelin, buserelin oestrogens, anabolic steroids
19
Q
renal tubular acidosis type 1
A
(distal)
inability to generate acid urine (secrete H+) in distal tubule
causes hypokalaemia
complications include nephrocalcinosis and renal stones
causes include idiopathic, rheumatoid arthritis, SLE, Sjogren’s, amphotericin B toxicity, analgesic nephropathy
20
Q
renal tubular acidosis type 2
A
(proximal)
decreased HCO3- reabsorption in proximal tubule
causes hypokalaemia
complications include osteomalacia
causes include idiopathic, as part of Fanconi syndrome, Wilson’s disease, cystinosis, outdated tetracyclines, carbonic anhydrase inhibitors (acetazolamide, topiramate)
21
Q
rental tubular acidosis type 3
A
(mixed)
extremely rare
caused by carbonic anhydrase II deficiency
results in hypokalaemia
22
Q
renal tubular acidosis type 4
A
(hyperkalaemic)
reduction in aldosterone leads in turn to a reduction in proximal tubular ammonium excretion
causes hyperkalaemia
causes include hypoaldosteronism, diabetes
23
Q
stess urinary incontinance Mx
A
pelvic floor muscle training: NICE recommend at least 8 contractions performed 3 times per day for a minimum of 3 months
surgical procedures: e.g. retropubic mid-urethral tape procedures
duloxetine may be offered to women if they decline surgical procedures
a combined noradrenaline and serotonin reuptake inhibitor
mechanism of action: increased synaptic concentration of noradrenaline and serotonin within the pudendal nerve → increased stimulation of urethral striated muscles within the sphincter → enhanced
contraction
24
Q
urge incontinance management
A
bladder retraining (lasts for a minimum of 6 weeks, the idea is to gradually increase the intervals between voiding) bladder stabilising drugs: antimuscarinics are first-line. NICE recommend oxybutynin (immediate release), tolterodine (immediate release) or darifenacin (once daily preparation). Immediate release oxybutynin should, however, be avoided in 'frail older women' mirabegron (a beta-3 agonist) may be useful if there is concern about anticholinergic side-effects in frail elderly patients
25
causes of hypocalcaemia
vitamin D deficiency (osteomalacia)
chronic kidney disease
hypoparathyroidism (e.g. post thyroid/parathyroid surgery)
pseudohypoparathyroidism (target cells insensitive to PTH)
rhabdomyolysis (initial stages)
magnesium deficiency (due to end organ PTH resistance)
massive blood transfusion
acute pancreatitis
Contamination of blood samples with EDTA may also give falsely low calcium levels.
26
Hypocalcaemia Mx
acute management of severe hypocalcaemia is with intravenous replacement. The preferred method is with intravenous calcium gluconate, 10ml of 10% solution over 10 minutes
intravenous calcium chloride is more likely to cause local irritation
ECG monitoring is recommended
further management depends on the underlying cause
27
osteomalacia bloods
hypocalcaemia associated with a low serum phosphate
28
phaeochromocytoma
rare catecholamine secreting tumour. About 10% are familial and may be associated with MEN type II, neurofibromatosis and von Hippel-Lindau syndrome
Basics
bilateral in 10%
malignant in 10%
extra-adrenal in 10% (most common site = organ of Zuckerkandl, adjacent to the bifurcation of the aorta)
1,2,3
NF-1, MEN 2, VHL (chromosome 3)
29
phaeochromocytoma features
```
hypertension (around 90% of cases, may be sustained)
headaches
palpitations
sweating
anxiety
```
30
phaeochromocytoma Ix
24 hr urinary collection of metanephrines (sensitivity 97%*)
| this has replaced a 24 hr urinary collection of catecholamines (sensitivity 86%)
31
phaeochromocytoma Mx
Surgery is the definitive management. The patient must first however be stabilized with medical management:
alpha-blocker (e.g. phenoxybenzamine), given before a
beta-blocker (e.g. propranolol)
32
thyroid function in pregnancy
In pregnancy, there is an increase in the levels of thyroxine-binding globulin (TBG). This causes an increase in the levels of total thyroxine but does not affect the free thyroxine level.
33
causes of lower than expected HBA1c
reduced lifespan of RBCs
Sickle-cell anaemia
GP6D deficiency
Hereditary spherocytosis
34
causes of higher than expected HBA1c
increased RBC lifespan
Vitamin B12/folic acid deficiency
Iron-deficiency anaemia
Splenectomy
35
gliptin MoA
DPP-4 inhibitors increase levels of incretins (GLP-1 and GIP)
oral preparation
trials to date show that the drugs are relatively well tolerated with no increased incidence of hypoglycaemia
do not cause weight gain
36
hypercalcaemia management
The initial management of hypercalcaemia is rehydration with normal saline, typically 3-4 litres/day. Following rehydration bisphosphonates may be used. They typically take 2-3 days to work with maximal effect being seen at 7 days
Other options include:
calcitonin - quicker effect than bisphosphonates
steroids in sarcoidosis
Loop diuretics such as furosemide are sometimes used in hypercalcaemia, particularly in patients who cannot tolerate aggressive fluid rehydration. However, they should be used with caution as they may worsen electrolyte derangement and volume depletion.
37
primary prevention statins
NICE recommend we use the QRISK2 CVD risk assessment tool for patients aged <= 84 years. Patients >= 85 years are at high risk of CVD due to their age. QRISK2 should not be used in the following situations as there are more specific guidelines for these patient groups:
type 1 diabetics
patients with an estimated glomerular filtration rate (eGFR) less than 60 ml/min and/or albuminuria
patients with a history of familial hyperlipidaemia
>10% = treat
38
QRISK 2 underestimates in who?
people treated for HIV
people with serious mental health problems
people taking medicines that can cause dyslipidaemia such as antipsychotics, corticosteroids or immunosuppressant drugs
people with autoimmune disorders/systemic inflammatory disorders such as systemic lupus erythematosus
39
criteria for starting statin in T1 diabetes
older than 40 years, or
have had diabetes for more than 10 years or
have established nephropathy or
have other CVD risk factors
40
statin monitoring
NICE recommend we follow-up patients at 3 months
repeat a full lipid profile
if the non-HDL cholesterol has not fallen by at least 40% concordance and lifestyle changes should be discussed with the patient
NICE recommend we consider increasing the dose of atorvastatin up to 80mg
41
neuropathic pain Mx
BPH/or any cause of urinary retention ... exclude amitryp
Renal impairment make pregab prefered over gaba
narrow-angle glaucoma exclude dulox and ami.
42
addisons features
lethargy, weakness, anorexia, nausea & vomiting, weight loss, 'salt-craving'
hyperpigmentation (especially palmar creases)*, vitiligo, loss of pubic hair in women, hypotension, hypoglycaemia
hyponatraemia and hyperkalaemia may be seen
crisis: collapse, shock, pyrexia
43
causes of hypoadrenalism
```
Primary causes
tuberculosis
metastases (e.g. bronchial carcinoma)
meningococcal septicaemia (Waterhouse-Friderichsen syndrome)
HIV
antiphospholipid syndrome
```
```
Secondary causes
pituitary disorders (e.g. tumours, irradiation, infiltration)
```
Exogenous glucocorticoid therapy
*Primary Addison's is associated with hyperpigmentation whereas secondary adrenal insufficiency is not
44
options for treating Graves
titration of anti-thyroid drugs (ATDs, for example carbimazole), block-and-replace regimes, radioiodine treatment and surgery. Propranolol is often given initially to block adrenergic effects
45
ADT titration
carbimazole is started at 40mg and reduced gradually to maintain euthyroidism
typically continued for 12-18 months
patients following an ATD titration regime have been shown to suffer fewer side-effects than those on a block-and-replace regime
46
block-and-replace
carbimazole is started at 40mg
thyroxine is added when the patient is euthyroid
treatment typically lasts for 6-9 months
47
side effects of carbimazole
agranulocytosis
48
radioiodine treatment
contraindications include pregnancy (should be avoided for 4-6 months following treatment) and age < 16 years. Thyroid eye disease is a relative contraindication, as it may worsen the condition
the proportion of patients who become hypothyroid depends on the dose given, but as a rule the majority of patient will require thyroxine supplementation after 5 years
49
graves features
Graves' disease is the most common cause of thyrotoxicosis. It is typically seen in women aged 30-50 years.
Features
typical features of thyrotoxicosis
specific signs limited to Grave's (see below)
```
Features seen in Graves' but not in other causes of thyrotoxicosis
eye signs (30% of patients)
exophthalmos
ophthalmoplegia
pretibial myxoedema
thyroid acropachy, a triad of:
digital clubbing
soft tissue swelling of the hands and feet
periosteal new bone formation
```
50
graves autoantibodies
TSH receptor stimulating antibodies (90%)
| anti-thyroid peroxidase antibodies (75%)
51
thyroid acropachy triad
digital clubbing
soft tissue swelling of the hands and feet
periosteal new bone formation
52
what is primary hyperaldosteronism?
Primary hyperaldosteronism was previously thought to be most commonly caused by an adrenal adenoma, termed Conn's syndrome. However, recent studies have shown that bilateral idiopathic adrenal hyperplasia is the cause in up to 70% of cases. Differentiating between the two is important as this determines treatment. Adrenal carcinoma is an extremely rare cause of primary hyperaldosteronism
53
Conns syndrome features
```
hypertension
hypokalaemia
e.g. muscle weakness
this is a classical feature in exams but studies suggest this is seen in only 10-40% of patients
alkalosis
```
54
conns syndrome Investigations
the 2016 Endocrine Society recommend that a plasma aldosterone/renin ratio is the first-line investigation in suspected primary hyperaldosteronism
should show high aldosterone levels alongside low renin levels (negative feedback due to sodium retention from aldosterone)
following this a high-resolution CT abdomen and adrenal vein sampling is used to differentiate between unilateral and bilateral sources of aldosterone excess
Adrenal Venous Sampling (AVS) can be done to identify the gland secreting excess hormone in primary hyperaldosteronism
55
conns syndrome Mx
adrenal adenoma: surgery
| bilateral adrenocortical hyperplasia: aldosterone antagonist e.g. spironolactone
56
HRT complications
increased risk of breast cancer
increased by the addition of a progestogen
in the Women's Health Initiative (WHI) study there was a relative risk of 1.26 at 5 years of developing breast cancer
the increased risk relates to the duration of use
the risk of breast cancer begins to decline when HRT is stopped and by 5 years it reaches the same level as in women who have never taken HRT
increased risk of endometrial cancer
oestrogen by itself should not be given as HRT to women with a womb
reduced by the addition of a progestogen but not eliminated completely
the BNF states that the additional risk is eliminated if a progestogen is given continuously
increased risk of venous thromboembolism
increased by the addition of a progestogen
transdermal HRT does not appear to increase the risk of VTE
NICE state women requesting HRT who are at high risk for VTE should be referred to haematology before starting any treatment (even transdermal)
increased risk of stroke
increased risk of ischaemic heart disease if taken more than 10 years after menopause
57
Indications for surgery primary hyperparathyroidism
Age under 50 years.
Adjusted serum calcium concentration that is 0.25 mmol/L or more above the upper end of the reference range.
Estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m2 although this threshold depends on other factors, such as age.
Renal stones or presence of nephrocalcinosis on ultrasound or CT.
Presence of osteoporosis or osteoporotic fracture.
Symptomatic disease
58
causes of primary hyperparathyroidism
80%: solitary adenoma
15%: hyperplasia
4%: multiple adenoma
1%: carcinoma
59
Ix hyperparathyroisism
raised calcium, low phosphate
PTH may be raised or (inappropriately, given the raised calcium) normal
technetium-MIBI subtraction scan
pepperpot skull is a characteristic X-ray finding of hyperparathyroidism
60
Mx hyperparathyroidism
the definitive management is total parathyroidectomy
conservative management may be offered if the calcium level is less than 0.25 mmol/L above the upper limit of normal AND the patient is > 50 years AND there is no evidence of end-organ damage
calcimimetic agents such as cinacalcet are sometimes used in patients who are unsuitable for surgery
61
fenofibrate MoA
Fibrates work through activating PPAR alpha receptors resulting in an increase in LPL activity reducing triglyceride levels.
62
fenofibrate ADR
gastrointestinal side-effects are common
| increased risk of thromboembolism
63
familial hypercholesterolaemia inheritance
AD
64
what is pseudohyperkalaemia?
Pseudohyperkalaemia is a rise in serum potassium that occurs due to excessive leakage of potassium from cells, during or after blood is taken. It is a laboratory artefact and does not represent the true serum potassium concentration. The majority of potassium is intracellular and thus leakage from cells can significantly impact serum levels. In this case the potassium is released as the large numbers of platelets aggregate and degranulate.
Causes include:
haemolysis during venepuncture (excessive vacuum of blood drawing or too fine a needle gauge)
delay in the processing of the blood specimen
abnormally high numbers of platelets, leukocytes, or erythrocytes (such as myeloproliferative disorders)
familial causes
65
sick euthyroid
In sick euthyroid syndrome (now referred to as non-thyroidal illness) it is often said that everything (TSH, thyroxine and T3) is low. In the majority of cases however the TSH level is within the >normal range (inappropriately normal given the low thyroxine and T3).
Changes are reversible upon recovery from the systemic illness and hence no treatment is usually needed.
66
insulinoma diagnosis
supervised, prolonged fasting (up to 72 hours)
| CT pancreas
67
insulinoma Mx
surgery
| diazoxide and somatostatin if patients are not candidates for surgery
68
what is MODY
Maturity-onset diabetes of the young (MODY) is characterised by the development of type 2 diabetes mellitus in patients < 25 years old. It is typically inherited as an autosomal dominant condition. Over six different genetic mutations have so far been identified as leading to MODY.
It is thought that around 1-2% of patients with diabetes mellitus have MODY, and around 90% are misclassified as having either type 1 or type 2 diabetes mellitus.
69
MODY features
typically develops in patients < 25 years
a family history of early onset diabetes is often present
ketosis is not a feature at presentation
patients with the most common form are very sensitive to sulfonylureas, insulin is not usually necessary
70
MODY types
MODY 3
60% of cases
due to a defect in the HNF-1 alpha gene
is associated with an increased risk of HCC
MODY 2
20% of cases
due to a defect in the glucokinase gene
MODY 5
rare
due to a defect in the HNF-1 beta gene
liver and renal cysts
71
what is an insulin stress test
Basics
used in investigation of hypopituitarism
IV insulin given, GH and cortisol levels measured
with normal pituitary function GH and cortisol should rise
Contraindications
epilepsy
ischaemic heart disease
adrenal insufficiency
72
hashimotos features
features of hypothyroidism
goitre: firm, non-tender
anti-thyroid peroxidase (TPO) and also anti-thyroglobulin (Tg) antibodies
Hashimoto's thyroiditis = hypothyroidism + goitre + anti-TPO
73
hashimotos associations
other autoimmune conditions e.g. coeliac disease, type 1 diabetes mellitus, vitiligo
Hashimoto's thyroiditis is associated with the development of MALT lymphoma
74
Liddles syndrome
gain of function ENa+ channel ( which increases intake of Na+ to inside thus followed by water )
L FOR LOW POTASSIUM
L FOR LOW H+ INSIDE ( ALKALOSIS)
L FOR LOW RENIN ( LIDDLE IS ONLY LOW RENIN HYPERTENSION IN WHOLE MEDICINE)
L FOR LOW CHANCES OF DEHYDRATION
75
congenital adrenal hyperplasia
group of autosomal recessive disorders
affect adrenal steroid biosynthesis
in response to resultant low cortisol levels the anterior pituitary secretes high levels of ACTH
ACTH stimulates the production of adrenal androgens that may virilize a female infant
76
causes of congenital adrenal hyperplasia
21-hydroxylase deficiency (90%)
11-beta hydroxylase deficiency (5%)
17-hydroxylase deficiency (very rare)
77
most common thyroid cancer
Papillary 70% Often young females - excellent prognosis
Usually contain a mixture of papillary and colloidal filled follicles
Histologically tumour has papillary projections and pale empty nuclei
Seldom encapsulated
Lymph node metastasis predominate
Haematogenous metastasis rare
78
what is medullary cancer
Cancer of parafollicular (C) cells, secrete calcitonin, part of MEN-2
C cells derived from neural crest and not thyroid tissue
Serum calcitonin levels often raised
Familial genetic disease accounts for up to 20% cases
Both lymphatic and haematogenous metastasis are recognised, nodal disease is associated with a very poor prognosis.
79
stridor thyroid cancer
Anaplastic 1% Not responsive to treatment, can cause pressure symptoms
Most common in elderly females
Local invasion is a common feature
Treatment is by resection where possible, palliation may be achieved through isthmusectomy and radiotherapy. Chemotherapy is ineffective.
80
follicular adenoma
Usually present as a solitary thyroid nodule
| Malignancy can only be excluded on formal histological assessment
81
follicular carcinoma
May appear macroscopically encapsulated, microscopically capsular invasion is seen. Without this finding the lesion is a follicular adenoma.
Vascular invasion predominates
Multifocal disease raree
82
autoimmune polyendocrine syndrome
is associated with other endocrine deficiencies in approximately 10% of patients
83
APS type 1
APS type 1 is occasionally referred to as Multiple Endocrine Deficiency Autoimmune Candidiasis (MEDAC). It is a very rare autosomal recessive disorder caused by mutation of AIRE1 gene on chromosome 21
Features of APS type 1 (2 out of 3 needed)
chronic mucocutaneous candidiasis (typically first feature as young child)
Addison's disease
primary hypoparathyroidism
Vitiligo can occur in both types
84
APS type 2
APS type 2 has a polygenic inheritance and is linked to HLA DR3/DR4. Patients have Addison's disease plus either:
type 1 diabetes mellitus
autoimmune thyroid disease
85
what is cushings syndrome
Investigations are divided into confirming Cushing's syndrome and then localising the lesion. A hypokalaemic metabolic alkalosis may be seen, along with impaired glucose tolerance. Ectopic ACTH secretion (e.g. secondary to small cell lung cancer) is characteristically associated with very low potassium levels. An insulin stress test is used to differentiate between true Cushing's and pseudo-Cushing's
86
cushings syndrome tests
overnight dexamethasone suppression test (most sensitive)
| 24 hr urinary free cortisol
87
how to localise cushings
The first-line localisation is 9am and midnight plasma ACTH (and cortisol) levels. If ACTH is suppressed then a non-ACTH dependent cause is likely such as an adrenal adenoma
Both low- and high-dose dexamethasone suppression tests may be used to localise the pathology resulting in Cushing's syndrome
88
dexamethosone supression test Normal
Cortisol following
low-dose dexamethasone
↓
Cortisol following
high-dose dexamethasone
↓
ACTH
↔
89
dexamethosone supression test in cushings syndrome due to cushings disease
Cortisol following
low-dose dexamethasone
↔
Cortisol following
high-dose dexamethasone
↓
ACTH
↑
90
dexamethosone supression test in cushings syndrome due to other causes
Cortisol following
low-dose dexamethasone
↔
Cortisol following
high-dose dexamethasone
↔
ACTH
↓
91
dexamethosone supression test in cushings syndrome due to ectopic ACTH
Cortisol following
low-dose dexamethasone
↔
Cortisol following
high-dose dexamethasone
↔
ACTH
↑
92
Kallmann's syndrome
Kallmann's syndrome is a recognised cause of delayed puberty secondary to hypogonadotropic hypogonadism. It is usually inherited as an X-linked recessive trait. Kallmann's syndrome is thought to be caused by failure of GnRH-secreting neurons to migrate to the hypothalamus.
The clue given in many questions is lack of smell (anosmia) in a boy with delayed puberty.
Features
'delayed puberty'
hypogonadism, cryptorchidism
anosmia
sex hormone levels are low
LH, FSH levels are inappropriately low/normal
patients are typically of normal or above average height
Cleft lip/palate and visual/hearing defects are also seen in some patients
93
thyroid eye disease pathophysiology
it is thought to be caused by an autoimmune response against an autoantigen, possibly the TSH receptor → retro-orbital inflammation
the inflammation results in glycosaminoglycan and collagen deposition in the muscles
94
thyroid eye disease prevention
smoking is the most important modifiable risk factor for the development of thyroid eye disease
radioiodine treatment may increase the inflammatory symptoms seen in thyroid eye disease. In a recent study of patients with Graves' disease around 15% developed, or had worsening of, eye disease. Prednisolone may help reduce the risk
95
thyroid eye disease management
topical lubricants may be needed to help prevent corneal inflammation caused by exposure
steroids
radiotherapy
surgery
96
Addisons investigations
In a patient with suspected Addison's disease the definite investigation is an ACTH stimulation test (short Synacthen test). Plasma cortisol is measured before and 30 minutes after giving Synacthen 250ug IM. Adrenal autoantibodies such as anti-21-hydroxylase may also be demonstrated.
If an ACTH stimulation test is not readily available (e.g. in primary care) then sending a 9 am serum cortisol can be useful:
> 500 nmol/l makes Addison's very unlikely
< 100 nmol/l is definitely abnormal
100-500 nmol/l should prompt a ACTH stimulation test to be performed
97
Addisons electrolyte imbalance
```
Associated electrolyte abnormalities are seen in around one-third of undiagnosed patients:
hyperkalaemia
hyponatraemia
hypoglycaemia
metabolic acidosis
```
98
gastroparesis T1 diabetes
symptoms include erratic blood glucose control, bloating and vomiting
management options include metoclopramide, domperidone or erythromycin (prokinetic agents)
99
thyrotoxic storm Mx
symptomatic treatment e.g. paracetamol
treatment of underlying precipitating event
beta-blockers: typically IV propranolol
anti-thyroid drugs: e.g. methimazole or propylthiouracil
Lugol's iodine
dexamethasone - e.g. 4mg IV qds - blocks the conversion of T4 to T3
100
thyrotoxic storm features
```
fever > 38.5ºC
tachycardia
confusion and agitation
nausea and vomiting
hypertension
heart failure
abnormal liver function test - jaundice may be seen clinically
```
101
what is lkatent autoimmune diabetes of adulthood?
The majority of patients with autoimmune-related diabetes present younger in life. There are however a small group of patients who develop such problems later in life. These patients are often misdiagnosed as having T2DM
102
what is Bartter's syndrome
Bartter's syndrome is an inherited cause (usually autosomal recessive) of severe hypokalaemia due to defective chloride absorption at the Na+ K+ 2Cl- cotransporter (NKCC2) in the ascending loop of Henle. It should be noted that it is associated with normotension (unlike other endocrine causes of hypokalaemia such as Conn's, Cushing's and Liddle's syndrome which are associated with hypertension).
Loop diuretics work by inhibiting NKCC2 - think of Bartter's syndrome as like taking large doses of furosemide
```
Features
usually presents in childhood, e.g. Failure to thrive
polyuria, polydipsia
hypokalaemia
normotension
weakness
```
103
tumors in MEN 1
3 P's
Parathyroid (95%): hyperparathyroidism due to parathyroid hyperplasia
Pituitary (70%)
Pancreas (50%): e.g. insulinoma, gastrinoma (leading to recurrent peptic ulceration)
Also: adrenal and thyroid
MEN 1 gene
104
tumours in MEN 2a
Medullary thyroid cancer (70%)
2 P's
Parathyroid (60%)
Phaeochromocytoma
RET oncogene
105
tumours is MEN 2b
Medullary thyroid cancer
1 P
Phaeochromocytoma
Marfanoid body habitus
Neuromas
RET 2
106
acromegaly features
coarse facial appearance, spade-like hands, increase in shoe size
large tongue, prognathism, interdental spaces
excessive sweating and oily skin: caused by sweat gland hypertrophy
features of pituitary tumour: hypopituitarism, headaches, bitemporal hemianopia
raised prolactin in 1/3 of cases → galactorrhoea
6% of patients have MEN-1
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acromegaly complications
hypertension
diabetes (>10%)
cardiomyopathy
colorectal cancer
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causes of raised prolactin
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prolactinoma
pregnancy
oestrogens
physiological: stress, exercise, sleep
acromegaly: 1/3 of patients
polycystic ovarian syndrome
primary hypothyroidism (due to thyrotrophin releasing hormone (TRH) stimulating prolactin release)
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Drug causes of raised prolactin
metoclopramide, domperidone
phenothiazines
haloperidol
very rare: SSRIs, opioids
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toxic multinodular goitre
Toxic multinodular goitre describes a thyroid gland that contains a number of autonomously functioning thyroid nodules resulting in hyperthyroidism.
Nuclear scintigraphy reveals patchy uptake.
The treatment of choice is radioiodine therapy.
110
Acromegaly management
Trans-sphenoidal surgery is the first-line treatment for acromegaly in the majority of patients.
If a pituitary tumour is inoperable or surgery unsuccessful then medication may be indicated:
somatostatin analogue
directly inhibits the release of growth hormone
for example octreotide
effective in 50-70% of patients
pegvisomant
GH receptor antagonist - prevents dimerization of the GH receptor
once daily s/c administration
very effective - decreases IGF-1 levels in 90% of patients to normal
doesn't reduce tumour volume therefore surgery still needed if mass effect
dopamine agonists
for example bromocriptine
the first effective medical treatment for acromegaly, however now superseded by somatostatin analogues
effective only in a minority of patients
External irradiation is sometimes used for older patients or following failed surgical/medical treatment
