Pathologies Flashcards
(107 cards)
1
Q
Aetiology Diabetes Mellitus; Type I
A
- not entirely known
- genes so far = molecules that help T cells recognise self antigens from non-self; Human Leukocyte Antigen (HLA)
- type I cannot distinguish own cells from others causing autoimmune attack on islets -> lymphocyte infiltration islets -> destruction B cells
- environmental factors + genes results in dec insulin, in glucose
2
Q
Aetiology Hyperinsulinaemia (prior to Diabetes Mellitus Type II)
A
- not entirely known
- combo of reduced tissue sensitivity to insulin and inability to secrete high levels of insulin
- failure B cells to meet inc demand for insulin in body
- ENV; expanded upper body visceral fat mass (pot belly) due to inc food, lack exercise
- inc FFAs in blood, dec insulin receptor sensitivity, dec Glc removal from blood
- more insulin req to get same amount glucose from blood (PERSON NOT DIABETIC)
3
Q
Diabetes Mellitus; long-term complications
A
Annual mortality is 5.4% - double rate non-diabetics
Life expectancy decreased by 5-10 years
MI commonest COD
Occur regardless of cause of DM, result from prolonged (5-10 years) poor glycaemic control
Main complication is damage to vessels; large vessel and small vessel disease
- Large vessel; accelerates atherosclerosis (many proposed mechanisms i.e. glucoses attach to LDL)
- Small vessel; molecules flux into subendothelial space, but find it hard to flux back to blood so buildup of trapped molecules
HD, MI and atherothrombotic stroke much more common in DM. Also neuropathy, nephropathy and retinopathy.
4
Q
What environmental factors are considered to be involved in Type 1 Diabetes Mellitus?
A
- ? chemicals
- ? bacteria in gut altered in infancy
- ? viral infection -
?molecules on viral surface mimic molecules on outside of B cells
5
Q
Aetiology Diabetes Mellitus Type II
A
- Pot bellied people need to develop hyperinsulinaemia to get same amount Glc
- gene controls insulin secretion
- variants of gen, some controlling whether or not you can secrete large amounts insulin
- If gene is a variant, may promote insulin prod low levels, but not high
- implicated genes are for “high end” insulin secretion, not central adiposity or periph ins resistance
- if only a few abnormal then able secrete lots insulin, but if many gene variants then unable to
6
Q
How is atherosclerosis accelerated in DM?
A
- Glc molecules stop LDL binding to its receptor (liver cells) tightly
- LDL not removed by lipid cells –> lipoprotein and lipid stay in blood –> hyperlipidaemia –> atherosclerosis
7
Q
Diabetes Mellitus Type II Treatment
A
Initial = trying to restore insulin sensitivity with exercise and dietary change
Oral hypoglycaemic drugs
- Metformin first-line; inhibits hepatic gluconeogenesis and antagonises action of glucagon
Sulphonylureas are a class of drug which act to close ATPK channels in B cells, stimulating calcium entry and thus insulin secretion
8
Q
Congenital Hypothyroidism
A
1/4000 births
Causes;
- athyreosis/hypoplastic/ectopic
- dyshormogenic
newborn screening and start treatment within first two weeks
9
Q
Acquired Hypothyroidism
A
Most common cause; Autoimmune (Hashimoto’s) thyroiditis
FH of thyroid/autoimmune disorders
Childhood issues
- lack of height gain
- pubertal delay (or precocity)
- poor school performance but work steadily
10
Q
Define Diabetes Mellitus
A
a group of metabolic diseases of multiple aetiologies characterised by hyperglycaemia together with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion/action/both
11
Q
What are symptoms of hyperglycaemia?
A
Polydipsia, polyuria, blurred vision, weight loss, infections
12
Q
How is diabetes diagnosed?
A
Measuring blood Glc or HbA1c
- fasting glc >/eq 7.0 mmol/l
- random glc >/eq 11.1 mmol/l
- HbA1c >/eq 48 mmol/mol
ONE diagnostic lab glucose plus symptoms or TWO diagnostic lab glucose or HbA1c levels without symptoms
13
Q
What are types of glycaemia?
A
- normoglycaemia = glc levels assoc w/low risk developing diabetes or CVD
- Intermediate Hyperglycaemia = group higher risk future diabetes and CVD
- Diabetes diagnostic hyperlycaemia = group sig inc premature mortality and inc risk microvascular and CV complications
14
Q
When can HbA1c not be used in DM diagnosis?
A
- children and young people
- pregnancy (current or recent <2months)
- short duration diabetes symptoms
- patients at high risk diabetes or acutely ill
- patient on med which may cause rapid glc rise (can be used if taking long term i.e. over 2 months)
- acute pancreatic damage or surgery
- renal failure
- HIV infection
15
Q
Clinical presentation type 1 diabetes mellitus
A
Short duration of
- thirst
- tiredness
- polyuria/nocturia
- weight loss
- blurred vision
- abdominal pain
On examination
- ketone breath
- dehydration
- inc resp rate, tachycardia, hypotension
- low grade infections; thrush/balamitis
16
Q
Clinical presentation type 2 diabetes mellitus
A
MAY HAVE NO SYMPTOMS
- thirst
- tiredness
- polyuria/nocturia
- sometimes weight loss
- blurred vision
- symptoms of complications i.e. CVD
Signs
- not ketotic
- usually overweight but not always
- low grade infections; thrush/balanitis
- micro/macrovascular complications
17
Q
What is MODY?
A
Genetically inherited form of diabetes - autosomal dominant
Types
- HNF1alpha; 70% cases, lowers amount insulin made by pancreas.
- HNF4alpha; generally treated with sulphonylurea tablet but progress onto insulin
- HNF1beta; generally develops later, treated with insulin. Typically have other complications i.e. renal cysts at birth
- glucokinase; mutation allows blood glc to be higher than usual. Diet treatment, complications rare
18
Q
Pheochromocytoma
A
Rare neuroendocrine tumour in adrenal medulla
Results in XS catecholamines
- inc HR leads to inc CO, leads to very inc blood pressure
19
Q
Describe biochemical tests involved in the diagnosis of diabetes
A
Random Venous plasma Glc ≥ 11.1mmol/L
Fasting plasma glucose ≥ 7.0 mmol/L
2 hr plasma Glc ≥ 11.1mmol/L in OGTT
HbA1c ≥ 48mmol/mol (Type 2 only)
If asymptomatic, requires confirmation by repeat testing on another day
20
Q
When should HbA1c not be used to diagnose diabetes?
A
- children and young people
- suspected type 1
- symptoms <2mnths
- high risk patients who are acutely ill
- patients taking meds that may cause rapid glc rise e.g. steroids
- acute pancreatic change
- pregnancy
- presence genetic, haematological or illness related factors affecting HbA1c and its measurement
21
Q
Acute diabetes monitoring
A
Point of care testing
Urine testing
- glycosuria
- ketonuria
Glucose-meter; measurement of blood capillary glucose
22
Q
What is factitious hypoglycaamia?
A
High insulin levels in absence of elevated C-peptide concentrations
23
Q
What is insulinoma?
A
insulin-secreting tumour
measure c-peptide levels
24
Q
Describe monitoring of chronic diabetes
A
Glucose; self-monitoring of blood glucose
HbA1c; glycaemic control
Urine albumin/creatinine ratio; diabetic renal disease - microvascular screening)
Lipids; macrovascular screening
25
What are macrovascular complications of diabetes?
- Coronary vascular disease
- Cerebrovascular disease
- Peripheral vascular disease
26
What are microvascular complications of diabetes?
- Retinopathy
- Neuropathy
- Nephropathy
27
Describe atherosclerosis in diabetes
Dyslipidaemia present nearly all patients
HDL cholesterol lower, triglycerides higher, LDL cholesterol in form small dense particles (worse; oxidation of these promotes features leading to plaque formation)
Endothelial dysfunction
Hypercoagulability
Can cause; strokes, angina, MI, heart failure, lower limb ischaemia --> ulcers (amputations are potential outcome)
Prevention = good diabetes control, bp control, lipid control, smoking cessation, weight, exercise
28
Describe retinopathy in diabetes
Non-proliferative Diabetic retinopathy;
- retinal capillary dysfunction, platelet dysfunction, blood viscosity abnormality
Proliferative Diabetic Retinopathy;
- retinal ischaemi, new blood vessel formation, vitreous haemorrhage, retinal tears/detachment
- treatment with laser photocoagulation
29
Describe nephropathy in diabetes
Microalbuminuria (leak of albumin) starts
Glomerular basement membrane changes, medangial tissue proliferation, "glomerular hypertension" all contribute to renal dysfunction
Progressive renal impairment (kidneys do not shrink)
Progressive renal failure to end-stage disease if unchecked
Prevention; screening urine for albumin
Control; Renin-angiotensin system blockade i.e. ACEI, angiotensin receptor blockade, renal inhibition
Hypertension control
30
Describe neuropathy in diabetes
Sensory, motor, autonomic
Sensory; objective loss, esp in feet and lower legs, subjective symptoms esp paresthesia
Autonomic; GI effects, CV effects (tachycardia, bp fluctuations), be aware of silent MI
31
Describe metformin
Biguanide, 1st line option
Improves insulin sensitivity;
- affects glucose production, decrease FA synthesis
- improves receptor function
- inhibits gluconeogenic pathways
Half life 6 hours
Pros; improves CV outcomes, cheap, efficaceous, normally well-tolerated, not associated with weight gain
Cons; risk of lactic acidosis by inhibiting lactic acid uptake by liver, GI side effects, risk vit B12 malabsorption
32
Describe sulphonylureas
2nd line option after lifestyle changes and metformin
increase insulin release;
- bind to sulphonylurea receptors on functioning pancreatic Beta cells
- binding closes ATP K channels
- decreased K influx, depolarises
- Ca channels open, influx calcium
- insulin release
Pros; used with metformin, rapid improvement in control, rapid improvement in symptomatic, rapid titration, cheap, generally well-tolerated
Cons; risk hypo, weight gain, caution in renal/hepatic disease, CI bleeding in pregnancy and breastfeeding,
33
Describe thiazolidinediones
2nd line option
(if hypo a concern and no congective cardiac failure)
Improves insulin action
- selectively stim nuclear receptor and modulates transcription insulin-sensitive genes
- reduces insulin tissue resistance in liver and peripheral tissues
- increases expense insulin-dependent glucose
- decreases withdrawal glucose from liver
- reduces glucose, insulin and glycated haemoglibin in blood
Pros; good if insulin resistance significant, cheap, CV safety established
Cons; increased bladder cancer risk, fluid retention, weight gain, small inc risk fractures in females
34
Clinical features of acromegaly
Hyperproduction GH
Soft tissue overgrowth
- spade like hands
- wide feet
- coarse facial features
- thick lips and tongue
- carpal tunnel syndrome
- sweating
Complications
- headaches
- chiasmal compression
- diabetes mellitus
- hypertension
- cardiomyopathy
- sleep apnoea
- accelerated OA
- cardiac polyps & CA
35
Diagnosis of acromegaly
Is there a pituitary tumour on MRI?
Is IGF-1 elevated?
Is rest of pituitary function normal?
36
Describe the hormone in excess in Cushing's syndrome
= excess corticosteroids (CORTISOL)
- tissue breakdown causes skin, muscle and bone weakness
- sodium retention may cause hypertension and heart failure
- insulin antagonism may cause diabetes mellitus
NOT ALWAYS DUE TO A PITUITARY TUMOUR; can be ACTH-dependent (pit tumour/ectopic) or independent (functioning adrenal adenoma)
37
Clinical signs of Cushing's
High value; Skin atrophy, spontaenous pupura, proximal myopathy, osteoporosis, growth arrest in children
Intermediate value; pink striae, facial mooning and hirsutism, oedema
central obesity, hypertension
38
Clinical signs of hyperprolactinaemia
Women
- galactorrhoea
- menstrual irregularity
- infertility
Men
- galactorrhoea (rare)
- impotence
- visual field abnormalities
- headache
- extraocular muscle weakness
- AP malfunction
39
Causes of hyperprolactinaemia
Physiological
- pregnancy, lactation, stres
Pharmacological
- DA depleting and DA antagonist drugs
Pathological
- primary hypothyroidism
- pituitary lesions (prolactinoma or pituitary "stalk pressure"
40
Drugs causing hyperprolactinaemia
Dopamine antagonists
DA depleting agents
Oestrogens
Some antidepressants
41
Clinical features of hypopituitarism
Adults
- tiredness, weight gin, depression, reduced libido, impotence, menstrual problems
- skin pallor
- reduced body hair
Children
- reduced linear growth
- delayed puberty
42
How are pituitary hypersecretions managed?
Prolactinoma
- dopamine agonists
Acromegaly
- somatostatin analogues
- GH receptor antagonist
43
How are pituitary hyposecretions managed?
- cortisol, T4, sex steroids, GH
| - desmopressin (vasopressin analogue)
44
Addison's Disease
Primary adrenal insufficiency
weakness, fatigue, anorexia, weight loss, skin pigmentation or vitiligo, hypotension, unexplained vomiting or diarrhoea, salt craving, postural symptoms
adrenal insufficiency tetss; ACTH test (synacthen test)
Random cortisol; >550nmol/l (not addison's), <550nmol/l (adrenal status uncertain)
if suspicions high and patient unwell, treat with steroids and do Synacthen test later
treatment = replace glucocorticoids, also replace mineralocorticoids
45
Clues to diagnosis of adrenal failure
- disproportion between illness severity & circulatory collapse/hypotension/dehydration
- unexplained hypoglycaemia
- other endocrine features (hypothyroidism, body hair loss, amenorrhoea)
- previous depression/weight loss
46
Describe glucocorticoid replacement
Hydrocortisone = 20 -30mg
Prednisolone = 7.5mg
Dexamethasone - 0.75mg
These will be given in divided doses to mimic normal diurnal variation
47
Describe mineracocorticoid replacement
Synthetic steroid, fludrocortisone
binds to mineralocorticoid (aldosterone) receptors
50-300mg daily
Adjust dose according to;
- clinical status
- U&E
- plasma renin level
48
What patients taking steroids need special care?
- hypoadrenal patients on replacement steroids
- patients on steroids in doses sufficient to suppress pituitary adrenal axis (>7.5mg prednisolone daily)
- patients who have received such treatment during the last 18 months
49
If stressed, how do you alter replacement of glucocorticoid?
minor illness or stress;
- double glucocorticoid
Major illness or surgery;
- 100mg hydrocortisone IV stat
- 50-100mg HC IV hourly
- as stress abates, reduced HD by 50% per day until back to usual replacement dose
50
Self-care rules for patients on steroids
Never miss a dose
Double HC dose in event of intercurrent illness
If severe vomiting or diarrhoea, call help immediately (likely need IM HC)
51
Endocrine causes of hypertension
Primary hyperaldosteronism
- unilateral adnoma, bilateral hyperplasia
Rarer causes
- phaechromocytoma
- Cushing's
- Acromegaly
- Hyperparathyroidism
- Hypothyroidism
- Congenital Adrenal Hyperplasia
52
Screening for Cushing's Syndrome
24hr Urinary free cortisol
- normal 14-135nmol/24h
1mg overnight dexamethasone suppression test taken at midnight
- normal <50nmol/l at 0900
53
Key points in hypothyroidism
- weight gain
- lethargy
- feeling cold
- constipation
- heavy periods
- dry skin/hair
- bradycardia
- slow reflexed
- goitre
- severe; puffy face, large tongue, hoarseness, coma
54
Key points in hyperthyroidism
- weight loss
- anxiety/irritability
- heat intolerance
- bowel frequency
- light periods
- sweaty palms
- palpitations
- hyperreflexia/tremors
- goitre
- thyroid eye symptoms/signs
55
Causes of congenital primary hypothyroidism
Developmental
- agenesis/maldevelopment
Dysphormogenesis
- trapping
- organification
- dehalogenase
56
Causes of acquired primary hypothyroidism
Autoimmune thyroid disease
- Hashimoto's
- atrophic
Iatrogenic
- post-op/post radioactive iodine
- external RT head and neck cancers
- antithyroid drugs
Chronic iodine deficiency
Post sub-acute thyroiditis
- post-partum thyroiditis
57
Causes of secondary/tertiary hypothyroidism
Pituitary/hypothalamic damage
- pit tumour
- craniopharyngioma
- post pit surgery/radiotherapy
- Sheehan's syndrome
- isolated TRH deficiency
58
Investigation and treatment of hypothyroidism
Investigation
- TSH/fT4
- Autoantibodies (TPO)
- FBC; MCV increased
- Lipids; hypercholesterolaemia
- Hyponatremia due to SIADH
- Increased muscle enzymes - - - ALT, CK
- hyperprolactinaemia
treatment
- levothyroxine; initial dose 50mcg/day, inrease after 2weeks to 100mcg
- increase dose until TSH normal
- after stabilisation annual testing
59
Solitary thyroid nodule investigations
Thyroid function test
US; benign v malignant
FNA
Isotope scanning if low TSH
60
Medullary thyroid cancer (lymphoma)
tumour arise from parafollicular cells
70% sporadic, 30% associated with MEN2, familial, mutations in RET oncogene
Serum calcitonin raised (as it releases calcitonin)
Treatment; total thyroidectomy, no role for radioiodine
Prognosis varies
61
Grave's Disease
autoimmune driven condition
- thyroid peroxidase antibodies
- tsh receptor antibodies
- review personal/fam history for concurrent autoimmune disease
62
Antithyroid drugs
Carbimazole, propylthiouracil
Side effects; rash, agranulocytosis (potentially fatal)
Titration regime or block and replace
63
Types of hypothyroidism
Primary (thyroid)
- Raised TSH, low FT3/FT4
Subclinical (compensated)
- Rasied TSH, normal FT3/FT4
Secondary (pituitary)
- Low TSH, low FT3/FT4
64
Prevalence of hypothyroidism
Commonest endocrine condition after diabetes
1.9% women, 0.1% men
Subclinical = 5% (10% of women >60)
Incidence of congenital 1 in 3500 births
65
Goitre Causes
Physiological
- puberty, pregnancy
Autoimmune
- Hashimoto's, Grave's
Thyroiditis
- acute (de Quervain's)
- chronic fibrotic (Reidel's)
Iodine deficiency (endemic goitre)
Dyshormogenesis
Goitrogens
66
Goitre Types
Multinodular
Diffuse
- colloid
- simple
Cysts
Tumours
- Adenomas
- carcinoma
- lymphoma
Miscellaneous
- sarcoidosis, tuberculosis
67
Solitary Nodule of Thyroid
Risk of malignancy
- child
- adults <30 or >60
- previous head/neck irradiation
- pain, cervical lymphadenopathy
Large dominant nodule of MNG also need investigations
5% chance malignancy
68
What is a hot/cold nodule?
Hot = Autonomous thyroid nodule, low risk cancer
Cold = non-functioning thyroid nodule, high risk cancer
69
Thyroid cancer
DIFFERENTIATED:
- Papillary; commonest, usaulyl <50yrs, multifocal, local spread to lymph nodes, assoc. with exposure to ionising radiation, genetics BRAF mutation or RET/PTC gene rearrangement good prognosis
- Follicular; usually single lesion, metastases to lung/bone, good prognosis if resectable
OTHER
- Anaplastic; <5% of thyroid cancers, agressive, locally invasive, very poor prognosis
- Lymphoma; rare
Prognosis poorer if
- age <16 or >45, tumour size, spread outside thyroid capsule and mets, TNM stage
70
Thyroid cancer management
```
Near total thyroidectomy
High dose radioiodine (ablative)
Long term suppressive doses thyroxine
Follow up
- thyroglobulin
- whole body iodide scanning (following 2-4 weeks thyroxine withdrawal or recombinant TSH injections)
```
71
What are complications of radioiodine?
>5/6 doses can cause leukaemia
Must stay away from children (<18) for 4 weeks
May develop eye disease
72
Causes of thyrotoxosis
Primary
- Grave's Disease (70%)
- Toxic MDN (20%)
Secondary
- pituitary adenoma secreting TSH
Thyrotoxicosis without hyperthyroidism
- destructive thyroiditis (post-partum, subacute, amiodarone-induced)
- excessive thyroxine administration
73
Treatment of hyperthyroidism
Beta blocker for symptoms i.e. tremor
Radioiodine, surgery (preferably only in large goitres), anti-thyroid drugs
74
Subclinical Hyperthyroidism
TSH suppressed
Normal free thyroid hormones
Concerns;
- bone
- AF
Treatment ATD/RAI if presistent
75
Hashimoto's thyroiditis
F>M 45-65 yrs
Autoimmune destruction thyroid epithelial cells
Cytotoxic T cells, cytokine and antibody mediated destruction
Circulating antibodies to thyroglobulin, thyroid peroxidase
76
How does a MNG most commonly form?
Iodine deficiency/goitrogens --> impaired synthesis of T3/T4 --> inc TSH --> hypertrophy and hyperplasia of epithelium
77
Histology of papillary carcinoma (of thyroid)
empty nuclei, psammoma bodies, may be cystic
78
Primary hyperparathyroidism
Often assymptomatic
| hypercalcaemia
79
Sporadic or familial parathyrdoid hyperfunction
MEN-1
- adenoma (85-95%)
- hyperplasia (5-10%)
- carcinoma (rare)
80
Secondary hyperparathyroidism
Physiological response to reduced Ca renal failure
81
Pituitary adenoma
Most common form of pituitary hyperfunction
Usuallt adults 35-60yrs, most sporadic, 5% ingerited eg. MEN1
Macroscopic;
- soft, well circumscribed lesion
- small microadenomas possible
Histology
- cels of same appearance as normal gland
- classified by hormones produced by neoplastic cells
Effects;
- prolactinoma; galactorrhea, menstrual disorders
- GH secreting; acromegaly, gigantism
- ACTH secreting; Cushing's syndrome
- Non-functioning; 25-50% detected tumours
82
Pituitary hypofunction
75% needs to be lost
Compression by tumours, trauma, infection (rare e.g. TB, sarcoidosis)
Post partum ischaemic necrosis = Sheehan's syndrome
83
Adrenal Hyperfunction
3 syndromes
Hypercortisolism; Cushing's syndrome
Hyperaldosteronism; Conn's Syndrome
Adrenogenital Syndrome
84
Hyperaldosteronism (Conn's)
Bilateral idiopathic hyperplasia
Functioning adrenal adenoma
(2ry due to dec renal perfusion, causing inc renin-angiotensin)
85
Adrenogenital syndromes
- functioning adrenal tumour
| - pituitary tumour (Cushing's)
86
What is an acute cause of adrenal insufficiency?
Destruction of gland due to meningococcal septicaemia
| - waterhouse friderichsen
87
Pheochromocytoma
Tumour of adrenal medulla
Secrete catecholamines; hypertension
Usually benign behaviour, may be bilateral
up to 25% inherited e.g. MEN2
10% extra adrenal
histology
- nests "Zellballen" of polygonal cells in vasc network
- granular cytoplasm containing catecholamines
88
Multiple endocrine neoplasia
Inherited disorders with underlying genetic conditions
hyperplasia/neoplasms of endocrine organs; younger age, multifocal
Several distinct syndromes
- MEN1 (Wermer syndrome)
- MEN2
89
Wermer Syndrome
MEN1 tumour suppressor gene mutation
Parathyroid hyperplasia and adenomas
Pancreatic and duodenal tumours (hypoglycaemia and ulcers)
Pituitary adenoma (prolactinoma)
*3Ps*
90
MEN2 syndrome
RET proto-oncogene mutations
- medullary carcinoma of thyroid
- phachromocytoma
MEN2A (Sipple syndrome)
+ Parathyroid hyperplasia
- extracellular domain auto dimerisation RET receptor
*2Ps + M*
MEN2B
+ neuromas of skin and mucous membrane, skeletal abnormalities
+ younger patients, aggressive
- autoactivation tyrosine kinase pathway
91
When is calcium low?
Serum calcium <2.2mmol/L
Symptoms at around 1.9mmol/L
92
What is Chvostek's and Trosseau's Sign?
Chvostek's
- Tap facial nerve whilst patient's face is relaxed, positive response is twitching of lip at corner of mouth
Trousseau's
- spasm due to inflation blood pressure cuff
INDICATIVE OF HYPOCALCAEMIA
93
Potential complication of thyroid surgery
Hoarse voice due to recurrent laryngeal nerve damage
94
What causes hypomagnesia?
Proton pump inhibitors
95
Important causes of hypocalcaemia
Post-surgical
| Vit D deficiency
96
Diagnostic approach in hypocalcaemia
History
- symptoms
- Ca and Vit D intake
- neck surgery
- autoimmune disorders
- meds
- FH
Examination
- neck scars
Investigations
- ECG
- serum calciun
- albumin
- phosphate
- PTH
- U&Es
- VitD
- Magnesium
97
Pseudohypoparathyroidism
Presents in childhood, group heterogeneous disroders defined by target organ unresposivesness to pTH
Hypocalcaemia, hypophosphataemia, elevated PTH
obesity, short stature and shortening of metacarpals may appear
98
Pseudo-pseudohypoparathyroidism
Obestiy, short stature and shortened metacarpals without abnormal calcium or PTH
99
Treatment of hypocalcaemia
Oral calcium
Post-thyroidectomy repeat calcium 24hr later
Vit D deficient, start vit D
If low Mg, stop any precipitating drug and replace Mg
100
Treatment severe hypocalcaemia
MEDICAL EMERGENCY
IV calcium gluconate
Calcium gluconate infusion
treat underlying cause
101
When are you hypercalcaemic?
<3mmol/L often asymptomatic, does usually require urgent correction
3-3.5mmol/L may be well tolerated bu can be symptomatic and prompt treatment usually indicated
>3.5mmol/L requires urgent correction die to risk dysrhythmia and coma
102
Clinical features hypercalcaemia
- Polyuria, polydipsia
- Anorexia, nausea and vomiting
- Bowel hypomotility and constipation
- Pancreatitis
- Peptic Ulcer disease
- Muscle weakness, bone pain, osteoporosis
- Decreased concentration, confusion
- shortened QT interval, bradycardia, hypertension
103
Hypercalcaemia diagnostic approach
History
- symptoms hypercalcaemia
- systemic inquiry
- meds
- FH
Exam
- lymph nodes
Concerns about maligancy
Investigations
- U&Es
- Ca
- PO4
- alk phos
- myeloma screen
- serum ACE
- PTH
104
Indications for surgery in hypercalcaemia
- presence symptoms
- serum calcium >0.25 above upper limit of normal
- osteoporosis or vertebral fracture
- eFGR<60 or kidney stones
- <50yrs
105
Diabetic foot disease
Charcot joint (arthropathy), ulceration, numbness
106
Describe the dexamethasone suppression test
Dexamethasone is steroid similar to cortisol so taking should lower ACTH (-ve feedback) and thus cortisol
Used to assess adrenal function
Usually used to diagnose Cushing's syndrome
- low dose determines if there is syndrome i.e. if cortisol is not suppressed by low dose, syndrome likely
- high dose can detect if problem is in the pituitary i.e. distinguish between disease and syndrome
In Cushing's disease, the low dose will not suppress, but high dose will suppress cortisol production (due to pituitary retaining some feedback control)
107
Describe the synacthen test
Synthetic ACTH
To aid Addison's diagnosis
Normally, after administration you would have cortisol rise, if low/absent cortisol rise then you may have Addison's or a pituitary problem
