Other Flashcards
(156 cards)
1
Q
What is the definition of hyperlactataemia and lactic acidosis?
A
Hyperlactatataemia = serum lactate >2
Lactic acidosis = serum lactate >4; even in the absence of overt acidemia
2
Q
How do you differentiate Type A from Type B Lactic Acidosis?
A
Type A Lactic Acidosis = caused by impaired tissue oxygenation
Type B Lactic acidosis = not caused by impaired tissue oxygenation
Therefore Type A usually has manifestations of hypoperfusion/shock incl reduced urine output, hypotension, cool or clammy extremities, altered mental status
3
Q
What are the main causes of Type B Lactic Acidosis?
A
1) Diabetes - secondary to ketoacidosis or metformin toxicity
2) Malignancy - incl lеukеmia, lymрhoma, and solid malignancies
3) Alcoholism - esp chronic, severe alcoholism
4) Methanol and ethylene glycol poisoning
5) HIV antiretroviral medication-induced mitochondrial dysfunction
6) Beta-adrenergic therapy - eg salbutamol
7) Inherited mitochondrial disorders eg MELAS (Mitochondrial Encephalopathy with Lactic Acidosis and Stroke-like episodes syndrome
8) Thiamine deficiency
9) Propofol therapy
10) Linezolid therapy
4
Q
What is Yellow Nail syndrome?
A
An uncommon disorder characterized by the triad of chronic lung disease; lymphedema; and slow-growing, yellow nails without a cuticle or lunula
Nails progressively thicken, becoming opaque and curved with loss of the lunula and cuticle
5
Q
What is Yellow Nail syndrome typically related to?
A
Chronic respiratory illness (esp pleural effusions and chronic bronchitis) and lymphoedema
Rarely assoc with RA, internal malignancy and immunodeficiency
6
Q
How do you treat Yellow Nail syndrome?
A
Treat underlying condition
Oral Vitamin E
Oral Zinc
Oral itraconazole
Most treatments disappointing
7
Q
What percentage of patients with pulmonary sarcoidosis have skin involvement?
A
20-30%
8
Q
What percentage of patients with cutaneous sarcoidosis have other organ involvement?
A
70%
9
Q
How do you treat cutaneous sarcoidosis?
A
Topical steroids
Consider MTx if severe
10
Q
What is cutaneous T cell lymphoma?
A
A diverse group of neoplasms of skin-homing T cells with great variation in appearance, histology, immunophenotype and prognosis
11
Q
What is the most common type of T cell lymphoma?
A
Mycosis fungoides - represents half of cases
12
Q
What is the classical presentation of mycosis fungoides?
A
Poikilodermatous patches and plaques typically in bathing-suit distribution
13
Q
What is the 5 year survival in Mycosis fungoides?
A
88%
14
Q
What are Neutrophilic Dermatoses?
A
A heterogenous group of disorders with overlapping clinical and histologic findings that are often assoc with internal diseases eg haem malignancy, dyscrasias, monoclonal gammopathy, IBD, RA
15
Q
What is the classic appearance of neutrophilic dermatoses?
A
Infiltrated papules, nodules, pustules +/- infiltrates affecting eyes, joints, bones, lung, liver, brain and lymph nodes
Key includes violaceous and undermined edges and display pathergy (trauma worsens extent of problem, so do not debride)
16
Q
What is Sweet Syndrome?
A
Acute febrile neutrophilic dermatosis
Infiltrated erythematous plaques and bullae favouring head/neck + constitutional symptoms
Most commonly secondary to AML, IBD, autoimmune disorders, drugs (azathioprine), pregnancy, infections (strep, GI yersiniosis)
17
Q
What is the treatment and prognosis of Sweet Syndrome?
A
Treat underlying condition
High dose steroids
Supportive tx of fever
Resoles in 5-12 weeks but may recur
18
Q
What is pyoderma gangrenosum?
A
The most common form of Neutrophilic Dermatosis
19
Q
What is Anetoderma?
A
Reactive phenomenon commonly assoc with autoimmune disorders (Graves, Lupus, Sjogren’s), HIV, leprosy, chickenpox, cutaneous B-cell lymphoma, infantile haemoangioma
Presents with focal atrophic plaques - buttonhole sign (on pinching)
Hard to treat
20
Q
What is Vitiligo?
A
Loss of melanocytes
Affects 0.5-1% of population
Assoc with autoimmune thyroid disease, T1DM, pernicious anaemia, Addison disease, SLE, RA, psoriasis, alopecia areata
21
Q
How do you treat Vitiligo?
A
Topical steroids or calcineurin inhibitors
Narrowband UVB
Sometimes in recalcitrant issues requires systemic steroids, surgical grafting, depigmentation therapy
Camouflage make-up
However not treating at all is also an option
22
Q
How does Cryoglobulinaemia present?
A
Acral cyanosis
Severe Raynaud’s with ulceration
Purpura
Livedo
Arterial thrombosis
Ulcers
Arthralgias/arthritis
May have systemic manifestations incl
membranoproliferative GN
Interstitial lung infiltrates
Sensory neuropathy
Abdominal pain
23
Q
What conditions is Cryoglobulinaemia assoc with?
A
Haematological malignancies incl multiple myeloma, CLL, Waldenstrom’s
Autoimmune incl RA, SLE, systemic sclerosis, vasculitis, glomerulonephritis
Infection - hep A/B/C
24
Q
How do you treat Cryoglobulinaemia?
A
Treat underlying condition
Keep warm
Rituximab for Hep-C assoc disease
Plasmapharesis + cytotoxic agent if life threatening complication
25
What are some of the skin diseases related to HIV?
Disseminated candidiasis
Seborrhoeic dermatitis
Oral hairy leukoplakia
Herpes zoster
Psoriasis (hard to treat)
Kaposi sarcoma
Eosinophilic folliculitis
Molluscum contagiosum
Cryptococcosis
Histoplasmosis
Large perianal HSV/CMV ulceres
26
What cutaneous reaction classically occurs with Zidovudine (for HIV tx)?
Nail dyspigmentation
27
What genotype is assoc with increased risk of DRESS syndrome?
HLA-B*5701
28
What genotype is assoc with increased risk of Steven Johnson Syndrome?
HLA-B*3505 in non-caucasians
29
What is erythema multiforme?
An acute self-limited disease characterised by abrupt onset of symmetrical fixed erythematous papules and target lesions
EM major - has mucosal involvement
EM minor - no mucosal involvement
30
What are the typical triggers/preceding infections for Erythema Multiforme?
HSV/VZV
Mycoplasma pneumoniae
EBV
CMV
Hepatitis
Parvovirus
HIV
31
How do you treat Erythema Multiforme?
Supportive treatment - usually resolves within 2-3 weeks
32
What is the difference between SJS and TEN?
SJS <10% BSA of epidermal detachment
TEN >10% BSA
33
What are the most commonly implicated drugs in SJS/TEN?
Allopurinol
NSAIDs
Antibiotics
Anticonvulsants
Onset is 7-21 days after commencing medication
34
How does SJS/TEN classically present?
Prodrome of URTI, fever, skin pain
Erythematous macules coalescing into sheets, duskiness
Mucosal involvement (usually painful)
Epidermal detachment (Nikolsky sign - skin desquamates when apply pressure to skin)
35
How do you treat SJS/TEN?
Immediate cessation of drug
Supportive care
IVIG
Analgesia
DVT prophylaxis
Mortality rate is 1-5% for SJS, 25-35% for TEN
36
What drug and what genotype are implicated in the classical association between Asian (esp Han chinese) and SJS/TEN ?
Carbamazepine
HLA-B*1502
37
What is erythema nodosum?
Inflammation of the fat, commonly affecting females between 20-40yo
Presents with tender bright red macules which fade to purple
Can have assoc fever, arthralgia, lethargy, abdo pain, diarrhoea
38
What conditions are assoc with Erythema Nodosum?
IBD
Sarcoidosis
Malignancy
Pregnancy
Infections - strep, TB, yersinia, mycoplasma
Medications - OCP
39
How do you diagnose erythema nodosum?
Clinical diagnosis
40
How do you treat Erythema Nodosum?
Treat underlying condition
Bed rest
Compression
Leg elevation
NSAIDs for pain
Takes 2-4 weeks to resolve
41
Asian patients with what polymorphism are at increased risk of phenytoin-induced DRESS syndrome?
CYP2C9*3
42
Han Chinese patients with what HLA gene are at increased risk of Allopurinol induced DRESS syndrome?
HLA-B*5801
43
What HLA allele is assoc with increased risk of Dapsone or Cotrimoxazole-induced DRESS syndrome?
HLA-B*13:01
44
What are the high risk drugs for DRESS syndrome?
Aromatic AEDs incl carbamazepine, phenytoin, Lamartine
Allopurinol
Vancomycin
Sulfonamide antibiotics
Anti-TB drugs
Dapsone
Mexilitine
Minocycline
45
What is the pathogenesis of DRESS syndrome?
Incompletely understood but thought to be T cell mediated hypersensitivity reaction
One part due to drug specific immune response
The other part is due to reactivation of viral infection involving the Herpesviridae family (eg, HHV-6, HHV-7, Epstein-Barr virus [EBV], cytomegalovirus [CMV])
46
What is the most common virus reactivated in association with DRESS syndrome?
HHV6
47
What is the typical latency period between drug exposure and symptom onset in DRESS syndrome?
2-8 weeks
48
What is the typical rash in DRESS syndrome?
A polymorphic evolving intensely erythematous maculopapular eruption that may progress to a coalescing erythema
Typically symmetrical and extensive involvement of trunk and arms with >50% of BSA
49
What symptom involving the face is often striking in patients with DRESS syndrome?
Facial oedema
50
Is mucosal involvement present in DRESS syndrome and if so, how does it compare to SJS/TEN?
Yes - but tends to be milder than SJS/TEN
51
Is eosinophilia required for the diagnosis of DRESS syndrome?
No - indeed it is not present in a significant subset of patients
52
What are the Systemic Symptoms in DRESS syndrome?
Fever
Lymphadenopathy
Haematological abnormalities
- eosinophilia
- elevated WCC (neu, lymph, mono)
- atypical lymphocytosis
However can also have Lymphopenia and thrombocytopenia
53
Is organ involvement common in DRESS syndrome?
Yes - 90% of affected patients have one organ involved, 30% have 2
54
What is the most common visceral organ involved in DRESS syndrome?
Liver - often manifests as mild, transient LFT derangement
55
What is the most common renal manifestation of DRESS syndrome?
Acute interstitial nephritis (10-30%)
56
Kidney involvement in DRESS is more common when associated with which medication?
Allopurinol
57
What is the most severe form of cardiac involvement in DRESS syndrome that is associated with a 50% mortality rate?
Acute necrotising eosinophilic myocarditis
58
What are the features of severe DRESS syndrome?
Significant Cytopenias / pancytopenia
Rapidly progressive/massive eosinophilia or atypical lymphocytosis
Major kidney failure
Liver enzymes >15x ULN
Other organ involvement eg heart, lungs, CNS
59
Viral reactivation of which virus is assoc with poorer prognosis in DRESS syndrome?
CMV
60
How long does the rash take to resolve in DRESS syndrome?
On average 7 weeks
61
What are some important points to remember about the diagnosis of DRESS syndrome?
important to recognize that DRESS is a dynamic process, and characteristic features are not all present concurrently. It is also possible, though uncommon, for patients with DRESS to have no or minimal cutaneous involvement (<5 percent), absent eosinophilia, and mild, systemic symptoms or organ involvement
62
What is the diagnostic criteria for DRESS syndrome?
The RegiSCAR score:
Fever
Lymphadenopathy
Eosinophilia
Atypical lymphocytes
Skin involvement
Organ involvement
Resolution >15 days
63
Which biomarker may be elevated in DRESS and can help differentiate it from SJS/TEN?
Thymus and Activation-Regulated Chemokine (TARC) level
64
Why is a skin biopsy performed in DRESS syndrome?
To exclude differentials - skin biopsy findings in DRESS are non specific
65
Which biomarker may be elevated in DRESS and can help differentiate it from SJS/TEN?
Thymus and Activation-Regulated Chemokine (TARC) level
66
Is patch testing helpful in DRESS syndrome?
May be positive in 30-60% and help establish drug causality
However invariably negative in allopurinol and sulfasalazine
67
What feature(s) may help differentiate DRESS syndrome from an Exanthematous drug reaction?
Systemic symptoms in exanthematous drug reactions tend to be mild and latency period shorter
68
How does Acute Generalised Exanthematous Pustolosis (AGEP) present?
AGEP presents with an extensive eruption of hundreds to thousands of pinpoint, nonfollicular pustules within hours of drug exposure
69
How do you treat DRESS syndrome?
Identify and cease offending drug
Supportive care
Mild-mod - topical steroids
Severe - systemic steroids
Refractory - cyclosporin, consider IVIG, IL-5, JAKi
70
What is the estimated mortality from DRESS syndrome?
2-10%
71
What is the prognosis of DRESS syndrome?
The majority of px recovering completely in weeks to months
However
- risk of death 2-10%
- risk of flares
- risk of relapse
- risk of autoimmune disease incl T1DM
72
What are SJS/TEN ?
severe cutaneous adverse reactions characterized by extensive necrosis and detachment of the epidermis. Mucous membranes are affected in more than 90 percent of patients, usually at two or more distinct sites
73
What defines SJS cf TEN?
SJS = <10% BSA
TEN = >30% BSA
10-30% BSA = SJS/TEN overlap
74
What are the risk factors for SJS/TEN?
HIV
Connective tissue disease
Malignancy
Older age
Black or Asian ethnicity
Renal impairment
75
What is the mortality of SJS/TEN?
23%
76
What drugs are strongly associated with SJS/TEN?
Similar to DRESS
Allopurinol
Lamotrigine
Phenytoin
Carbamazepine
Sulfasalazine
Sulfamethoxazole
Phenobarbital
Oxicam NSAIDs eg piroxicam
Immune checkpoint inhibitors
77
78
What are some of the key adverse effects from anticholinergic medications?
Blurred vision
Dry eyes
Dry mouth
Drowsiness
Confusion
Hallucinations
Tachycardia
Urinary retention
Constipation
Flushing
Anhidrosis
79
What psychiatric medications are more likely to cause hyponatraemia?
SSRIs
carbamazepine
Less likely TCAs, mirtazapine
80
What antipsychotic generally has fewest side effects?
Aripiprazole
81
82
What two antipsychotics are less likely to cause or aggravate Parkinsonism?
Clozapine
Quetiapine
83
What two antipsychotics tend to cause more weight gain / metabolic side effects?
Clozapine
Olanzapine
84
What medications are typically implicated in Neuroleptic Malignant Syndrome?
Antipsychotics
85
What are the cardinal signs of neuroleptic malignant syndrome?
Fever
Autonomic instability
Rigidity
Mental status changes
Elevated CK
elevated WCC
However no sign is pathognomonic and some px may not be experience full suite of signs (particularly if second gen antipsychotic)
86
How do you manage neuroleptic malignant syndrome?
Stop causative agent
Supportive care eg fluids
Muscle relaxants (eg dantrolene) and dopamine agonists (amantadine) if severe
87
What is the usual cause of serotonin toxicity?
Combining different agents that increase serotonin eg SSRIs, TCa, SNRI, opioids, antihistamines, amphetamines, cocaine, MAOIs, St. John’s wort, LSD, triptana
88
What are the typical features of serotonin syndrome?
Changes in mental state
Autonomic incl hyperthermia, shivering, mydriasis
Neurological incl myoclonus, clonus, hyperreflexia
89
What psychiatric meds are more likely to cause QTc prolongation?
Escitalopram
Citalopram
Quetiapine
Ziprasidone
90
What are the short term effects of hyperprolactinaemia?
Hypogonadism
Sexual dysfunction
Galactorrhoea
Gynecomastia
Altered menstrual cycle
91
What are the long term effects of hyperprolactinaemia?
Weight gain
Osteoporosis
Increased risk of breast, prostate and pituitary cancer,
Depression
cVD
92
What psych meds are most likely to cause hyperprolactinaemia?
First Gen antipsychotics eg haloperidol
Occ second gen antipsychotics eg risperidone, paliperidone
Very occ SSRIs
93
What is the management of hyperprolactinaemia caused by antipsychotic medications?
Switch to aripiprazole (D2 partial agonist) or cautious use of adjunctive dopamine agents (eg bromocriptine, amantadine, pramipexole)
94
What are side effects of Lithium?
Hypercalcaemia
Hyperparathyroidism
Hypothyroidism
Renal disease
- nephrogenic diabetes insipidus
- nephrotic syndrome
- renal tubular acidosis
- glomerulosclerosis
95
What signs may indicate lithium toxicity?
Confusion
GI distress
Coarse tremor
Sick sinus syndrome
Heart block
Reversible T wave changes
Very rarely - pseudotumour cerebri
96
What side effect of Clozapine is most likely to be fatal?
Constipation
97
What are the key side effects of Clozapine?
Constipation
Agranulocytosis
Myocarditis - first 2 months
Cardiomyopathy - beyond 3 mths
Drilling
Seizures
Enuresis
98
What side effects may antiepileptic mood stabilisers have?
Osteoporosis
PCOS (Valproate)
Hyperammonia (Valproate, Carbamazepine)
Leukopenia and thrombocytopenia (Valproate, Carbamazepine)
Hypersensitivity reactions or DRESS
Movement disorders
99
What are examples of CYP450 inducers?
Carbamazepine
St. John’s wort
Rifampicin
Phenytoin
Tobacco
Some steroids
100
What psychiatric drugs are excreted renally and therefore need to be used cautiously in renal impairment?
Lithium
Gabapentin/pregabalin
Topiramate
Paliperidone
101
What psychiatric drug is particularly implicated in causing Drug Induced Liver Injury?
Duloxetine
102
What psychiatric medications are contraindicated in someone with hepatitis?
Valproate
Carbamazepine
103
What psychiatric meds are contraindicated in patients with neutropenia?
Carbamazepine
Clozapine
104
What psychiatric drugs are contraindicated in patients with epilepsy?
Bupropion
Clozapine
105
What are the key teratogenic risks of valproate?
Neural tube defects 6%
Vit K def with third trimester exposure (resulting in preterm labour and bleeding risk)
106
Which medical conditions are assoc with high risk of suicide?
Huntingtons
Multiple sclerosis
Epilepsy
HIV
Malignancy
107
What is AIDS-assoc Kaposi Sarcoma?
A low-grade vascular tumor associated with infection with human herpesvirus 8 (HHV-8), also known as the KS-associated herpesvirus (KSHV).
variable clinical course, ranging from minimal disease presenting as an incidental finding to a rapidly progressing neoplasm that can result in significant morbidity and mortality, depending upon the specific sites of involvement
108
How do you treat AIDs-assoc Kaposi sarcoma?
ART
+
Consider local therapies including
Intralesional chemo
Radiotherapy
Topical imiquimod
Cryotherapy
Or if advanced/rapidly progressive KS then systemic therapy with doxorubucin
109
What is the most important mediator of keratinocyte death in SJS/TEN?
Granulysin
110
What is the specific antidote for severe methotrexate toxicity / overdose?
Glucarpidase
- carboxypeptidase G2 which metabolises MTX to inactive metabolites
- hard to get and very expensive
Alternative = ?dialysis
111
What is a Buruli ulcer?
A neglected tropical disease caused by environmental bacterium Mycobacterium ulcerans which infects the skin and subcutaneous tissue
112
How do you diagnose Buruli ulcers?
Clinically + PCR
113
How do you treat Buruli ulcers?
Rifampicin PLUS clarithromycin (or moxi/ciprofloxacin)
If Rifampicin contraindicated/not tolerated then Clarithromycin + Moxi/ciprofloxacin
114
What is one of the most important consequences of cortisol deficiency?
Loss of normal suppressive action of endogenous glucocorticoids on inflammatory cytokines (eg NF-kb)
115
What are risk factors to adrenal crisis?
Older age
Hx of prior adrenal crises
Presence of autoimmune polyglandular syndrome
T1DM
Non-endocrine conditions eg asthma, cardiac disease
116
Why might rates of adrenal crisis be increasing?
Due to current use of lower-dose short acting glucocorticoid regimens (eg hydrocortisone)
117
What is the mortality rate in adrenal crisis?
6%
118
What are the common precipitants of adrenal crisis?
Infections incl gastroenteritis
Serious injury
Major surgery
Minor procedures eg vaccination, zoledronic acid infusion
Certain meds eg immune checkpoint inhibitors (due to hypophysitis or adrenalitis)
Non-adherence to glucocorticoid replacement therapy
Undiagnosed coexisting thyrotoxicosis or initiation of thyroxine therapy in undiagnosed hypoadrenalism
CYP3A4 inducers such as carbamazepine, rifampicin, phenytoin, st john's wort - may increase hydrocortisone metabolism necessitating increase in glucocorticoid dose
119
How do you treat adrenal crisis?
IV hydrocortisone 100mg followed by 50mg Q6H + IV fluids
Hydrocortisone is preferred drug but
alternatively can use dex (4mg every 24hrs)
120
What should you advise px with hypoadrenalism about if they get sick?
2-3x dose (stress dose)
Administer it via IM/subcut if unable GI losses
121
Mutations in which gene result in 21-hydroxylase deficiency and classical congenital adrenal hyperplasia?
Mutations in CYP21A2
Found on chromosome 6
122
What is the most common cause of atypical genitalia in 46XX newborns and of primary adrenal insufficiency in childhood?
CAH
123
How common is classical and non-classical CAH?
Classical 1:10,000
Non-classical 1:200
124
10% of patients with CAH have CAH-X - what is this?
CAH + hypermobility-type Ehlers-Danlos syndrome due to contiguous gene deletion that disrupts both CYP21A2 and TNXB
125
What is the effect of 21-hydroxylase deficiency in CAH?
Cortisol precursors are shunted to produce androgen precursors eg 11beta-hydroxyandrostenedione
Extradrenal metabolism then converts these to androgens/potent agonists of androgen receptor
126
How are most px with CAH identified?
On newborn screening (based on elevated 17-OHP levels
Confirmed with Corticotropin stimulation test
127
How does classical CAH affect females and males?
Females - clitoromegaly, partially fused labial majora, urogenital sinus (spares uterus, fallopian tubes, ovaries)
Males - nil effects on sexual development
Approx 75% have salt-wasting adrenal crisis within first 3 weeks of birth
128
How does classic CAH present in post-pubertal patients?
Females - like PCOS - hirsutism, menstrual dysfunction, subfertility, recurrent miscarriages, acne
Males - oligospermia, may have testicular adrenal rest tumours, otherwise asymptomatic
Other features:
Early puberty
Accelerated childhood growth and early epiphyseal fusion
Short stature
Gonadal hypofunction and subfertility
Hyperpigmentation
Insulin resistance
Adrenal hyperplasia and tumours
Decreased adrenaline/cortisol secretion
129
Why are patients with CAH at increased risk of death?
From adrenal crisis
130
Why is short stature in CAH common?
Due to hyperandrogenism (of condition) plus long-term glucocorticoids which suppress growth (treatment related)
131
What is the carrier frequency for class CAH?
1 in 60
Consequently, without partner genotyping, risk of having child affected with classic CAH is 1 in120
132
What are testicular adrenal rest tumours and when do they develop in men with classic CAH?
Develop in 30-50% of adolescent boys/men with classic CAH particularly after periods of poor control and non-adherence to tx
Usually bilateral and arise from rete testis
Identified by US
Can cause irreversible damage to Sertoli cells -> male infertility
Treat with glucocorticoids to shrink tumour (if too big or fibrotic may require surgery)
133
How do we treat classic CAH?
Hydrocortisone (to counteract adrenal insufficiency)
134
How do we treat nonclassical CAH?
Women - glucocorticoid OR OCP + cyproterone/spiro
Men - nil required
135
What are the causes of subclinical hyperthyroidism?
Same as overt hyperthyroidism eg Graves, toxic MNG, toxic adenoma + excessive intake of exogenous levothyroxine
136
How might you differentiate exogenous from endogenous subclinical hyperthyroidism?
Exogenous - more common; T3 levels usually middle or lower part of reference range
Endogenous - T3 levels typically normal or high end of reference range
137
What is the hormone profile in subclinical hyperthyroidism?
Suppressed TSH
Normal FT4 and FT3
138
What are the potential clinical consequences of subclinical hyperthyroidism?
Progression to overt hyperthyroidism
CV disease eg AF, HF, death from CHD
Bone loss
Fractures
Dementia
139
What is the best predictor of progression from subclinical to overt hyperthyroidism?
Baseline TSH level
If <0.1 - higher risk/more likely to progress
140
What should you do if you find suppressed TSH but normal FT4/FT3?
Hx and ex
Repeat TFTs in 2-3 months time (50% will normalise)
If persistent - then evaluate further (eg TSH-RAb, USS or scintigraphy scan)
141
When should you treat subclinical hyperthyroidism?
>65yo
142
How do you treat subclinical hyperthyroidism?
1st line = methimazole, radioiodine or surgery
Graves <65yo - methimazole
Graves >65 - radioiodine or surgery
Toxic MNG or adenoma - radioiodine
Large goitre/compressive symptoms /hyperparathyroidism - surgery
143
When is radioiodine contraindicated in Graves' disease and why?
Active Graves' opthalmopathy - can worsen eye disease
144
What is the mechanism of trisomy 21 in 95% of cases?
Meiotic nondisjunction
145
What is transient abnormal myelopoiesis?
A form of myeloid preleukaemia seen in 10% of patients with Down syndrome; due to GATA1 mutations
Affects px before age 5, usually resolved spontaneously
146
What is the risk of leukaemia in px with Down syndrome?
2-3%
147
What is the most common form of congenital heart disease in Down syndrome?
ASD
148
What is the rate of pulmonary hypertension in Down syndrome?
5%
149
Most solid organ tumours are reduced in frequency in Down syndrome except for which type?
Testicular tumours
150
Dementia is more likely to occur in persons with Down syndrome who have what?
Seizures
151
What is the most common cause of death in persons with Down syndrome?
Respiratory infections, due in part to immunodeficiencies
152
What is Li Fraumeni syndrome?
An inherited autosomal dominant condition associated with predisposition to multiple malignancies at an early age
Also known as:
Sarcoma, Breast, Leukemia, and Adrenal Gland (SBLA) cancer syndrome and
as heritable tumor protein p53 gene (TP53)-related cancer syndrome
153
What are the key pathogenic variants found in Li-Fraumeni syndrome?
TP53
154
What treatment modality should you avoid in patients with Li-Fraumeni syndrome?
Radiation therapy
As they are more susceptible to radiation-associated cancers
155
What are the more common cancers seen in patients with Li-Fraumeni syndrome?
Sarcomas
Breast cancer
Brain cancer incl choroid plexus
Adrenocortical carcinomas
156
Aortic root repair is indicated in all symptomatic patients with Marfan syndrome as well as asymptomatic patients with an aortic diameter above what threshold?
>50mm
Although if rapid expansion, fhx, marked arterial tortuosity, diffuse aortic enlargement can consider at >45mm
