Endocrinology Flashcards
(159 cards)
1
Q
Main causes of hypercalcaemia
A
- Primary hyperparathyroidism: commonest cause in non-hospitalised patients
- Malignancy: the commonest cause in hospitalised patients. This may be due to number of processes, including; bone metastases, myeloma, PTHrP from squamous cell lung cancer
2
Q
Other causes of hypercalcaemia
A
sarcoidosis* vitamin D intoxication acromegaly thyrotoxicosis Milk-alkali syndrome drugs: thiazides, calcium containing antacids dehydration Addison's disease Paget's disease of the bone**
3
Q
Multiple endocrine neoplasia
Type 1
MEN1 gene
Most common presentation = hypercalcaemia
A
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
4
Q
Multiple endocrine neoplasia
Type 2a
RET oncogene
A
Medullary thyroid cancer (70%)
2 P’s
Parathyroid (60%)
Phaeochromocytoma
5
Q
Multiple endocrine neoplasia
Type 2b
RET oncogene
A
Medullary thyroid cancer
1 P
Phaeochromocytoma
Marfanoid body habitus
Neuromas
6
Q
Hypokalaemia with alkalosis
A
vomiting
thiazide and loop diuretics
Cushing’s syndrome
Conn’s syndrome (primary hyperaldosteronism)
7
Q
Hypokalaemia with acidosis
A
diarrhoea
renal tubular acidosis
acetazolamide
partially treated diabetic ketoacidosis
8
Q
acetazolamide
A
used to treat and prevent altitude sickness
9
Q
Mechanism of action of Thiazolidinediones
e.g. pioglitazone, rosiglitazone
A
They are agonists to the PPAR-gamma receptor and reduce peripheral insulin resistance
The PPAR-gamma receptor is an intracellular nuclear receptor. It’s natural ligands are free fatty acids and it is thought to control adipocyte differentiation and function.
10
Q
Adverse effects of thiazonlidinediones
A
weight gain
liver impairment: monitor LFTs
fluid retention - therefore contraindicated in heart failure. The risk of fluid retention is increased if the patient also takes insulin
recent studies have indicated an increased risk of fractures
bladder cancer: recent studies have shown an increased risk of bladder cancer in patients taking pioglitazone (hazard ratio 2.64)
11
Q
Renal tubular necrosis
Type 1 distal
A
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
12
Q
Renal tubular necrosis
Type 2 proximal
A
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)
13
Q
Renal tubular necrosis
Type 3 Mixed
A
extremely rare
caused by carbonic anhydrase II deficiency
results in hypokalaemia
14
Q
Renal Tubular necosis
Type 4 Hyperkalaemic
A
reduction in aldosterone leads in turn to a reduction in proximal tubular ammonium excretion
causes hyperkalaemia
causes include hypoaldosteronism, diabetes
15
Q
Hypothyroidism
Hashimoto’s
A
most common cause in the developed world
autoimmune disease, associated with type 1 diabetes mellitus, Addison’s or pernicious anaemia
may cause transient thyrotoxicosis in the acute phase
5-10 times more common in women
16
Q
Hyperthyroidism
thyroxicosis
A
most common cause of thyrotoxicosis
as well as typically features of thyrotoxicosis other features may be seen including thyroid eye disease
17
Q
Sub acute thyroiditis
de Quervain’s
A
hypothyroidism
associated with a painful goitre and raised ESR
18
Q
Reidel’s thyroiditis
A
fibrous tissue replacing the normal thyroid parenchyma
causes a painless goitre
19
Q
other causes of hypothyroidism
A
Postpartum thyroiditis
Drugs -lithium, amiodarone
Iodine deficiency
20
Q
other causes of hyperthyroidism
A
Toxic multinodular goitre
autonomously functioning thyroid nodules that secrete excess thyroid hormones
Drugs
amiodarone
21
Q
General features of hypothroidism
A
Cold intolerance
Weight gain
Lethargy
22
Q
General features of hyperthyroidism
A
Weight loss
‘Manic’, restlessness
Palpitations
Heat intolerance
23
Q
Skin changes in hypothyroidism
A
Dry (anhydrosis), cold, yellowish skin
Non-pitting oedema (e.g. hands, face)
Dry, coarse scalp hair, loss of lateral aspect of eyebrows
24
Q
Skin changes in hyperthyroidism
A
Increased sweating
Pretibial myxoedema: erythematous, oedematous lesions above the lateral malleoli
Thyroid acropachy: clubbing
25
Primary hyperaldosteronism
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
```
26
Primary hyperaldosteronism
Investigations
- plasma aldosterone/ renin ratio
high aldosterone, low renin
-CT
27
Faconi syndrome
rare disorder of renal function
| excess amounts of glucose, bicarb, phosphates, urate and certain amino acids are excreted in the urine.
28
Symptoms of faconi syndrome
kids - polydipsia, polyuria
| Adults - bone pain, muscle weakness
29
Treatment of faconi syndrome
- oral sodium bicarbonate
- bone disease - bisphosphonates and vit D
- renal transplant in kids
30
Thyroid cancer
papillary carcinoma
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
70% ( often young women, excellent prognosis)
31
Thyroid cancer
Follicular adenoma
Usually present as a solitary thyroid nodule
| Malignancy can only be excluded on formal histological assessment
32
thyroid cancer
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 rare
33
Thyroid cancer
Medullary carcinoma
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.
Cancer of parafollicular (C) cells, secrete calcitonin, part of MEN-2
34
Thyroid cancer
anaplastic carcinoma
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
35
thyroid cancer
lymphoma
associated with hashimoto's lymphoma
36
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
37
Management of hypocalcaemia
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
38
TFTs
| Thyrotoxicosis (e.g. Graves' disease)
TSH Low
| Free T4 High
39
```
TFTs
Primary hypothyroidism (e.g. Hashimoto's thyroiditis)
```
TSH High
| Free T4 Low
40
TFTs
| Secondary hypothyroidism
TSH Low
| Free T4 Low
41
TFTs
Sick euthyroid
TSH - low
Free T4 - low
Common in hospital inpatients. Changes are reversible upon recovery from the systemic illness and no treatment is usually needed
42
TFTs
Subclinical thyroiditis
TSH - High
Free T4 - Normal
This is a common finding and represents patients who are 'on the way' to developing hypothyroidism but still have normal thyroxine levels. Note how the TSH levels, as mentioned above, are a more sensitive and early marker of thyroid problems
43
TFTs
Poor thyroxine compliance
TSH High
Free T4 - normal
Patients who are poorly compliant may only take their thyroxine in the days before a routine blood test. The thyroxine levels are hence normal but the TSH 'lags' and reflects longer term low thyroxine levels
44
Hyponatraemia
Urinary sodium > 20 mmol/l
Sodium depletion, renal loss
diuretics: thiazides, loop diuretics
Addison's disease
diuretic stage of renal failure
45
Hyponatraemia
Urinary sodium > 20 mmol/l
Patient often euvolaemic
SIADH (urine osmolality > 500 mmol/kg)
| hypothyroidism
46
Hyponatraemia
Urinary sodium <20mmol/l
Sodium depletion, extra-renal loss
diarrhoea, vomiting, sweating
| burns, adenoma of rectum
47
Hyponatraemia
Urinary sodium <20mmol/l
Water excess (patient often hypervolaemic and oedematous)
secondary hyperaldosteronism: heart failure, liver cirrhosis
nephrotic syndrome
IV dextrose
psychogenic polydipsia
48
History of primary hyperparathyroidism
primary hyperparathyroidism is stereotypically seen in elderly females with an unquenchable thirst and an inappropriately normal or raised parathyroid hormone level. It is most commonly due to a solitary adenoma
49
Causes of primary hyperparathyroidism
80%: solitary adenoma
15%: hyperplasia
4%: multiple adenoma
1%: carcinoma
50
Features of primary hyperparathyroidism
```
polydipsia, polyuria
peptic ulceration/constipation/pancreatitis
bone pain/fracture
renal stones
depression
hypertension
```
51
Conditions associated with primary hyperparathyroidism
hypertension
| multiple endocrine neoplasia: MEN I and II
52
Investigations of primary hyperparathyroidism
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
53
Treatment of primary 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
54
Causes of hypokalaemia with acidosis
diarrhoea
renal tubular acidosis
acetazolamide
partially treated diabetic ketoacidosis
55
Causes of hypokalaemia with alkalosis
vomiting
thiazide and loop diuretics
Cushing's syndrome
Conn's syndrome (primary hyperaldosteronism)
56
Key features of MEN I
peptic ulceration, galactorrhoea, hypercalcaemia
57
Key features of MEN IIa
medullary thyroid cancer, hypercalcaemia, phaeochromocytoma
58
Key features of Liddle's syndrome
hypokalaemia, hypertension, alkalosis, family history of similar problems, low aldosterone
59
What is Liddle's syndrome
Liddle's syndrome is a rare autosomal dominant condition that causes hypertension and hypokalaemic alkalosis. It is thought to be caused by disordered sodium channels in the distal tubules leading to increased reabsorption of sodium.
Treatment is with either amiloride or triamterene
60
Thyroid cancer associatated with MEN-2
medullary thyroid cancer
61
Key features of Conn's syndrome
hypokalaemia, hypertension, alkalosis, no similar family history, raised aldosterone
62
Key features of Addisons
hyperkalaemia, hyponatraemia, hypoglycaemia
| hypotension, hyperpigmentation, lethargy
63
Stereotypical history of primary hyperaldosteronism
a 35-year-old woman is found to have a blood pressure of 180/110 mmHg. She complains of feeling tired and weak. Routine bloods show hypokalaemia
64
Stereotypical history of phaeochromocytoma
a 40-year-old patient with a history of hypertension presents with episodic palpitations, excessive sweating, headaches and tremor
65
Treatment of hyperaldosteronism
spironalactone
66
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
67
Investigations of acromegaly
Serum IGF-1 levels have now overtaken the oral glucose tolerance test (OGTT) with serial GH measurements as the first-line test. The OGTT test is recommended to confirm the diagnosis if IGF-1 levels are raised.
Growth hormone levels vary throughout the day so aren't useful
68
Acromegaly OGTT
in normal patients GH is suppressed to < 2 mu/L with hyperglycaemia
in acromegaly there is no suppression of GH
may also demonstrate impaired glucose tolerance which is associated with acromegaly
in normal patients GH is suppressed to < 2 mu/L with hyperglycaemia
in acromegaly there is no suppression of GH
may also demonstrate impaired glucose tolerance which is associated with acromegaly
69
Incretin effect
In normal physiology an oral glucose load results in a greater release of insulin than if the same load is given intravenously - this known as the incretin effect. This effect is largely mediated by GLP-1 and is known to be decreased in T2DM.
70
Glucagon-like peptide-1 (GLP-1) mimetics (e.g. exenatide, Liraglutide)
Exenatide is an example of a glucagon-like peptide-1 (GLP-1) mimetic. These drugs increase insulin secretion and inhibit glucagon secretion. One of the major advances of GLP-1 mimetics is that they typically result in weight loss
Given by SC injection
71
Dipeptidyl peptidase-4 (DPP-4) inhibitors (e.g. Vildagliptin, sitagliptin)
Key points
Dipeptidyl peptidase-4, DPP-4 inhibitors increase levels of incretins (GLP-1 and GIP) by decreasing their peripheral breakdown
oral preparation
trials to date show that the drugs are relatively well tolerated with no increased incidence of hypoglycaemia
do not cause weight gain
72
Features of Kallman's syndrome
'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
73
What is Kallman's syndrome
a recognised cause of delayed puberty secondary to hypogonadotrophic hypogonadism. It is usually inherited as an X-linked recessive trait. Kallman'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
74
Kleinfelter's syndrome
Klinefelter's syndrome is associated with karyotype 47, XXY
```
Features
often taller than average
lack of secondary sexual characteristics
small, firm testes
infertile
gynaecomastia - increased incidence of breast cancer
elevated gonadotrophin levels
```
75
What is androgen insensitivity syndrome
Androgen insensitivity syndrome is an X-linked recessive condition due to end-organ resistance to testosterone causing genotypically male children (46XY) to have a female phenotype. Complete androgen insensitivity syndrome is the new term for testicular feminisation syndrome
76
Features of androgen insensitivity syndrome
'primary amenorrhoea'
undescended testes causing groin swellings
breast development may occur as a result of conversion of testosterone to oestradiol
77
management of androgren insufficiency syndrome
```
counselling - raise child as female
bilateral orchidectomy (increased risk of testicular cancer due to undescended testes)
oestrogen therapy
```
78
What are thiazolidediones?
Thiazolidinediones are a class of agents used in the treatment of type 2 diabetes mellitus. They are agonists to the PPAR-gamma receptor and reduce peripheral insulin resistance. Rosiglitazone was withdrawn in 2010 following concerns about the cardiovascular side-effect profile.
79
Adverse effects of thiazolidediones
weight gain
liver impairment: monitor LFTs
fluid retention - therefore contraindicated in heart failure. The risk of fluid retention is increased if the patient also takes insulin
recent studies have indicated an increased risk of fractures
bladder cancer: recent studies have shown an increased risk of bladder cancer in patients taking pioglitazone (hazard ratio 2.64)
80
Primary hypoparathyroidism
decrease PTH secretion
e.g. secondary to thyroid surgery*
low calcium, high phosphate
treated with alfacalcidol
81
Symptoms of hypoparathyroidism secondary to hypocalcaemia
tetany: muscle twitching, cramping and spasm
perioral paraesthesia
Trousseau's sign: carpal spasm if the brachial artery occluded by inflating the blood pressure cuff and maintaining pressure above systolic
Chvostek's sign: tapping over parotid causes facial muscles to twitch
if chronic: depression, cataracts
ECG: prolonged QT interval
82
pseudohypoparathryroidism
target cells being insensitive to PTH
due to abnormality in a G protein
associated with low IQ, short stature, shortened 4th and 5th metacarpals
low calcium, high phosphate, high PTH
diagnosis is made by measuring urinary cAMP and phosphate levels following an infusion of PTH. In hypoparathyroidism this will cause an increase in both cAMP and phosphate levels. In pseudohypoparathyroidism type I neither cAMP nor phosphate levels are increased whilst in pseudohypoparathyroidism type II only cAMP rises.
83
pseudopsuedohypoparathyroidism
similar phenotype to pseudohypoparathyroidism but normal biochemistry
84
Risk factors for urinary incontinence
```
advancing age
previous pregnancy and childbirth
high body mass index
hysterectomy
family history
```
85
Classification of urinary incontinence
overactive bladder (OAB)/urge incontinence: due to detrusor overactivity
stress incontinence: leaking small amounts when coughing or laughing
mixed incontinence: both urge and stress
overflow incontinence: due to bladder outlet obstruction, e.g. due to prostate enlargement
86
Investigations of urinary incontinence
bladder diaries should be completed for a minimum of 3 days
vaginal examination to exclude pelvic organ prolapse and ability to initiate voluntary contraction of pelvic floor muscles ('Kegel' exercises)
urine dipstick and culture
urodynamic studies
87
Management of urinary incontinence
```
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
```
88
Management of stress incontinence
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
89
Risk factors for endometrial cancer
```
obesity
nulliparity
early menarche
late menopause
unopposed oestrogen. The addition of a progestogen to oestrogen reduces this risk (e.g. In HRT). The BNF states that the additional risk is eliminated if a progestogen is given continuously
diabetes mellitus
tamoxifen
polycystic ovarian syndrome
hereditary non-polyposis colorectal carcinoma
```
90
Features of endometrial cancer
postmenopausal bleeding is the classic symptom
premenopausal women may have a change intermenstrual bleeding
pain and discharge are unusual features
91
Investigations for endometrial cancer
women >= 55 years who present with postmenopausal bleeding should be referred using the suspected cancer pathway
first-line investigation is trans-vaginal ultrasound - a normal endometrial thickness (< 4 mm) has a high negative predictive value
hysteroscopy with endometrial biopsy
92
Management of endometrial cancer
localised disease is treated with total abdominal hysterectomy with bilateral salpingo-oophorectomy. Patients with high-risk disease may have post-operative radiotherapy
progestogen therapy is sometimes used in frail elderly women not consider suitable for surgery
93
What is ezetimibe
Ezetimibe is a lipid-lowering drug which inhibits cholesterol receptors on enterocytes, decreasing cholesterol absorption in the small intestine.
Ezetimibe monotherapy is recommended as an option for treating primary hypercholesterolaemia in adults in whom initial statin therapy is contraindicated or who cannot tolerate statin therapy
Ezetimibe, coadministered with initial statin therapy, is recommended as an option for treating primary hypercholesterolaemia in adults who have started statin therapy when:
serum total or LDL cholesterol concentration is not appropriately controlled either after appropriate dose titration of initial statin therapy or because dose titration is limited by intolerance to the initial statin therapy
a change from initial statin therapy to an alternative statin is being considered.
94
Management of acromegaly
1. Trans-sphenoid surgery
2. somatostatin analogue
directly inhibits the release of growth hormone
for example octreotide
effective in 50-70% of patients
3. 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
4. dopamine agonists
for example bromocriptine
the first effective medical treatment for acromegaly, however now superseded by somatostatin analogues
effective only in a minority of patient
95
What is Gitelman's syndrome
Gitelman's syndrome is due to a defect in the thiazide-sensitive Na+ Cl- transporter in the distal convoluted tubule.
96
Features of Gitelman's syndrome
```
normotension
hypokalaemia
hypocalciuria
hypomagnesaemia
metabolic alkalosis
```
97
Causes of Cushing's syndrome
ACTH dependent causes
Cushing's disease (80%): pituitary tumour secreting ACTH producing adrenal hyperplasia
ectopic ACTH production (5-10%): e.g. small cell lung cancer is the most common causes
98
Causes of Cushing's syndrome
ACTH independent causes
iatrogenic: steroids
adrenal adenoma (5-10%)
adrenal carcinoma (rare)
Carney complex: syndrome including cardiac myxoma
micronodular adrenal dysplasia (very rare)
99
Causes of Cushing's syndrome
Pseudo-Cushing's
mimics Cushing's
often due to alcohol excess or severe depression
causes false positive dexamethasone suppression test or 24 hr urinary free cortisol
insulin stress test may be used to differentiate
100
Congenital adrenal hyperplasia
21-hydroxylase deficiency features
virilisation of female genitalia
precocious puberty in males
60-70% of patients have a salt-losing crisis at 1-3 wks of age
101
Congenital adrenal hyperplasia
11-beta hydroxylase deficiency features
virilisation of female genitalia
precocious puberty in males
hypertension
hypokalaemia
102
Congenital adrenal hyperplasia
| 17-hydroxylase deficiency features
non-virilising in females
inter-sex in boys
hypertension
103
Endocrine side effects of corticosteroids
impaired glucose regulation, increased appetite/weight gain, hirsutism, hyperlipidaemia
104
Cushing side effects of corticosteroids
moon face, buffalo hump, striae
105
Musculoskeletal side effects of corticosteroids
osteoporosis, proximal myopathy, avascular necrosis of the femoral head
106
Immunosuppression side effects of corticosteroids
increased susceptibility to severe infection, reactivation of tuberculosis
107
Psychiatric side effects of corticosteroids
insomnia, mania, depression, psychosis
108
Gastro-intestinal side effects of corticosteroids
peptic ulceration, acute pancreatitis
109
Ophthalmic side effects of corticosteroids
glaucoma, cataracts
110
other side effects of corticosteroids
suppression of growth in children
intracranial hypertension
neutrophilia
111
Mineralocorticoid side-effects
fluid retention
| hypertension
112
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).
113
Barrter's syndrome features
```
usually presents in childhood, e.g. Failure to thrive
polyuria, polydipsia
hypokalaemia
normotension
weakness
```
114
What is Riedel's thyroiditis
Riedel's thyroiditis is a rare cause of hypothyroidism characterised by dense fibrous tissue replacing the normal thyroid parenchyma. On examination a hard, fixed, painless goitre is noted. It is usually seen in middle-aged women. It is associated with retroperitoneal fibrosis.
115
MODY 3
60% of cases
due to a defect in the HNF-1 alpha gene
is associated with an increased risk of HCC
116
MODY 2
20% of cases
| due to a defect in the glucokinase gene
117
MODY 5
rare
due to a defect in the HNF-1 beta gene
liver and renal cysts
118
Features of MODY
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
119
Features of phaeochromocytoma
```
Features are typically episodic
hypertension (around 90% of cases, may be sustained)
headaches
palpitations
sweating
anxiety
```
120
Management of phaeochromocytoma
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)
121
Investigations of phaeochromocytoma
24 hr urinary collection of metanephrines (sensitivity 97%*)
| this has replaced a 24 hr urinary collection of catecholamines (sensitivity 86%)
122
Features of Addison's
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
123
Mechanism of action: propylthiouracil
Blocks thyroid peroxidase from coupling and iodinating the tyrosine residues on thyroglobulin --> reducing thyroid hormone production + inhibits 5'-deiodinase which reduces peripheral conversion of T4 to T3
124
Stereotypical history of primary hyperaldosteronism
a 35-year-old woman is found to have a blood pressure of 180/110 mmHg. She complains of feeling tired and weak. Routine bloods show hypokalaemia
125
Stereotypical history of Addison's disease
a 40-year-old woman presents with lethargy, weakness and weight loss. On examination her blood pressure is 80/50 mmHg and there is hyperpigmentation of the skin
126
Features of primary hyperaldosteronism
```
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
```
127
Stereotypical history of 5-alpha reductase deficiency
a baby is born with ambiguous genitalia, exhibiting labioscrotal folds with clitoromegaly. At 13 years of age the child undergoes virilization with facial hair and deepening of the voice
128
Key features of Liddle's syndrome
hypokalaemia, hypertension, alkalosis, family history of similar problems, low aldosterone
129
Adverse effects of sulfonylureas
```
hypoglycaemia
weight gain
hyponatraemia
hepatotoxicity
bone marrow suppression
peripheral neuropathy
```
130
what are meglitinides
increase pancreatic insulin secretion
like sulfonylureas they bind to an ATP-dependent K+(KATP) channel on the cell membrane of pancreatic beta cells
often used for patients with an erratic lifestyle
adverse effects include weight gain and hypoglycaemia (less so than sulfonylureas)
131
Complications of subclinical hypothyroidism
Dementia
AF
osteoporosis
132
Mechanism of action: Gliptins (DPP-4 inhibitors)
Reduce the peripheral breakdown of incretins such as GLP-1
133
9am serum cortisol > 500 nmol/l
makes Addison's very unlikely
134
9am serum cortisol 100-500 nmol
Is inconclusive - needs short synacthen test
135
9am serum cortisol <100
Diagnosis of Addisons
136
Electrolyte abnormalities in addisons
hyperkalaemia
hyponatraemia
hypoglycaemia
metabolic acidosis
137
Management of acute hyponatraemia with severe symptoms (drunk, drinking lots, reduced GCS
Hypertonic saline (3%)
138
Management of hypervolaemic hyponatraemia
fluid restrict to 500–1000 mL/day
consider loop diuretics
consider vaptans
139
Management of euvolaemic hyponatraemia
fluid restrict to 500–1000 mL/day
consider medications:
demeclocycline
vaptans (vasopressin/ADH receptor antagonists) - can be hepatoxic and make pts thirstier
140
Management of hypovolaemic hyponatraemia
normal, i.e. isotonic, saline (0.9% NaCl)
this may sometimes be given as a trial
if the serum sodium rises this supports a diagnosis of hypovolemic hyponatraemia
if the serum sodium falls an alternative diagnosis such as SIADH is lik
141
Causes of pseudohyperkalaemia
- high blood cell turnover (e.g. essential thrombocytosis)
- haemolysis during sampling
- delayed processing
- familial causes
142
Features of a thyroid storm
```
fever > 38.5ºC
tachycardia
confusion and agitation
nausea and vomiting
hypertension
heart failure
abnormal liver function test - jaundice may be seen clinically
```
143
Management of thryroid storm
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
144
Thyroid MALT lymphoma
follows an indolent course and often presents as a neck lump without typical 'B' symptoms such as fever, night sweats and weight loss. Some patients may report compression symptoms such as dysphagia and dyspnoea.
145
Anosmia hypogonadotrophic hypogonadism
Kallman's syndrome
146
Features of Addison's
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
147
Secondary causes of hypertriglyceridaemia
```
diabetes mellitus (types 1 and 2)
obesity
alcohol
chronic renal failure
drugs: thiazides, non-selective beta-blockers, unopposed oestrogen
liver disease
```
148
secondary causes of hypercholesterolaemia
nephrotic syndrome
cholestasis
hypothyroidism
149
Indications for Meglitinides in T2DM
stimulate insulin release - good for erratic lifestyle- take them shortly before meals
150
Investigations of Cushing's
24 hour urine cortisol
151
Prolactin and Dopamine
Dopamine continuously suppresses prolactin
152
Geitelman's syndrome - features
normotension, hypokalaemia + hypocalciuria
hypomagnesaemia
metabolic alkalosis
153
Pathophysiology of Geitelman's syndrome
a defect in the thiazide-sensitive Na+ Cl- transporter in the distal convoluted tubule.
154
Features of primary hyperaldosteronism
hypertension
hypokalaemia - e.g. muscle weakness
alkalosis
bilateral idiopathic adrenal hyperplasia is the cause in up to 70% of cases
155
de Queverian's thryoiditis
sub acute hyperthyroiditis followed by hypothyroidism
156
Formula for working out averabge BM from HbA1c
average plasma glucose = (2 * HbA1c) - 4.5
157
Management of acromegaly: adjunct to surgery
Octreotide
158
Fibrates
Used in management of hyperlipidaemia
Increase risk of VTE
work through activating PPAR alpha receptors resulting in an increase in LPL activity reducing triglyceride levels.
159
Cause of congenital adrenal hyperplasia
due to 21-hydroxylase deficiency
