Adrenal Crisis

Addison's Disease

Anterior pituitary - ACTH, GH, FSH, LH, TSH, PRL

Posterior pituitary- ADH, oxytocin

Presentation

History of recent physical stress like stress, major injury, myocardial infarction 

Nausea and vomiting, muscle pains, confusion, coma, fatigue
Low BP or postural hypotension, tachycardia

Risk if ≥5 mg prednisolone equivalent for more than 4 weeks

Investigations

Hypoglycaemia
Low sodium

High potassium 

A patient with hypothyroidism feels worse on thyroxine

T1 DM with unexplained hypoglycaemia

Hyperuraemia
Hypercalcaemia
Metabolic acidosis
Random 9am cortisol  or short synacthen test - helps differentiate between primary and secondary adrenal insufficiency. 

Raised thyroid stimulating hormone (TSH)

Pathophysiology

Primary - disease affecting the adrenal gland  Addison's 

  Autoimmune 

  Infective (including TB, HIV and fungal) 

  Iatrogenic

  Haemorrhage or infarction (Waterhouse- Friedrichsen- meningococcemia)

  Malignant infiltration (metastasis, lymphoma) 

  Non malignant infiltration (sarcoidosis, haemochromatosis, amyloidosis)

  Genetic 

Secondary/Tertiary adrenal insufficiency (twice as common as addisons)

Panhypopituitarism

Pituitary apoplexy – infarction or hemorrhage of tumor

Chronic steroid therapy (suppresses HPA axis)

Tumors, granulomas

Treatment

1L/hour to maintain their BP

Hydrocortisone 100 mg with subsequent doses of 100 to 200 mg over 24 hours divided into three or four doses.

Look for and treat trigger 

Adrenal crisis. Do a random cortisol. Give steroids! ↓Na less likely unless SIADH, ↑K+ unlikely. #foamedhttps://t.co/K6h3shBZRJ pic.twitter.com/tTcoPehG3N

— South London EM FOAM (@slemfoam) June 15, 2017

Sick Day Rules
Double hydrocortisone if fever > 37.5 C or for infection or sepsis requiring an antibiotic

For severe nausea (often with a headache), 20 mg of hydrocortisone orally and sip rehydration or electrolyte fluids (such as dioralyte)

On vomiting, they should use their emergency injection if they have one (eg 100 mg of hydrocortisone) immediately. Then they should call a doctor, saying ‘Addison’s emergency’

They should take 20 mg of hydrocortisone orally immediately after a major injury to avoid shock

If patients have persistent vomiting or diarrhoea that is likely to interfere with absorption of medication or fluid balance, you should admit them to hospital for intravenous hydrocortisone

Some authors recommend that the dose of hydrocortisone should be increased (by 5 mg to 10 mg) before strenuous exercise.

Pituitary Apoplexy

Acute haemorrhagic or non-haemorrhagic necrosis of the pituitary gland. An existing pituitary macroadenoma is usually present (60-90%) but it can occur with healthy glands in few isolated cases. It is also more likely with medical treatment of a prolactinoma, pregnancy (Sheehan) and cerebral angiography, trauma and sudden changes in ICP.  

As the gland suddenly enlarges it may cause compression of structures adjacent to the sella leading to: 

  sudden headache

  loss of visual acuity with a chiasmal field defect

  oculomotor palsies (CN III) 

  Decreased level of consciousness, hypopituitanism, Addisonian crisis and subarachnoid irritation. 

Investigation

CT -  routine CT is insensitive to the diagnosis unless frank intracranial haemorrhage is present. The pituitary mass may be evident and be hyperdense. Fluid debris levels may also be evident. Useful to do to exclude a sub-arachnoid. 

MRI - typically demonstrates a pituitary region mass. Confirms the diagnosis in over 90% of patients. A pituitary CT is indicated if MRI is contraindicated or not possible.

Endocrine evaluation with blood samples for random serum cortisol, TSH, free T4, prolactin, IGF1, LH, FSH, testosterone (men), oestradiol (women) for later analysis

Hyponatraemia in 40% of cases 

Treatment

Hydrocortisone 100 mg i.m. bolus followed by 50–100 mg six hourly by intramuscular injection or 100–200 mg as an intravenous bolus followed by 2–4 mg per hour by continuous i.v. infusion can be used

Neurosurgical intervention should be considered in patients with:

   Severely reduced visual acuity

   Severe and persistent visual field defects

   Deteriorating level of consciousness

References 
https://lifeinthefastlane.com/ccc/adrenal-insufficency/

https://wikem.org/wiki/Adrenal_crisis

http://www.emdocs.net/em3am-acute-adrenal-insufficiency/

https://lifeinthefastlane.com/pediatric-perplexity-012/

http://sinaiem.org/tag/adrenal-crisis/

https://radiopaedia.org/articles/adrenal-insufficiency-1

http://www.emdocs.net/core-em-adrenal-crisis/

https://emsimcases.com/2017/02/14/adrenal-crisis/

http://www.endocrineconnections.com/content/5/5/G12

https://emedicine.medscape.com/article/765753-overview

http://learning.bmj.com/learning/module-intro/-diagnose-manage-adults-addison%27s-disease.html?moduleId=10013263&searchTerm=%E2%80%9Cadrenal%E2%80%9D&page=1&locale=en_GB

https://radiopaedia.org/articles/pituitary-apoplexy

http://www.endocrineconnections.com/content/5/5/G12.full

https://link.springer.com/article/10.1007/BF02112028

http://www.bmj.com/content/342/bmj.d1270

Hyperemesis Gravidarum

We all know that nausea and vomiting in pregnancy is common affecting 50–75% of pregnant women any time from the 4th week of pregnancy, most common in the 9th and 12 week, and we probably misdiagnose some of these people with hyperemesis gravidarum which affects less than 1%. To me, I'm not sure that the precise difference matters, as I think I'd struggle to send home a ketotic pregnant lady with at least some of the hyperemesis protocol...

Hyperemesis Gravidarum
Persistent, intractable nausea and vomiting beginning in the first trimester
Associated with a weight loss of >5% of pre-pregnancy weight
Dehydration, electrolyte imbalance and ketosis

Cause
Likely multifactorial - typically higher levels of human chorionic gonadotrophin
H. pylori may have a part to play
Make sure you exclude other causes - molar pregnancy is the most serious. These patients are unlikely to improve enough to be able to go home.

Treatment
Antiemetics:
Ginger - evidence base says ginger tablets improve symptoms in four days

Other:
Small meals (6 times a day). Eat as soon as you feel hungry. Avoid likely triggers - like fatty food.
Fluids- cold, clear, and carbonated like ginger ales and lemonades as well as smoothies or slushies.

Thiamine - thiamine requirements increase in pregnancy, so give if "prolonged" vomiting. Some say if no meal in a weak, others say vomiting for more than three weeks.
Oral thiamine 100mg / day, or IV thiamine (pabrinex is OK, but does have other B vitamins). Toxbase suggests overdose of thiamine is low risk.

Antiacids- treat non ulcer dyspepsia if there are signs of it. PPIs are thought to be safe. There is some evidence that H. pylori increases vomiting, so if the patient has prolonged vomiting, consider

Corticosteroids - can be used as a third line. I'd like O&G do that bit.

Patient Advice 
No proven effects on the fetus, except fetal growth restriction, pre-term delivery. The pregnancy may be complicated by triploidy, trisomy 21 and hydrops fetalis. It may be due to a molar pregnancy.
Mum can get problems from electrolyte derangement - wernickes, central pontine myelinolysis due to hyponatraemia, ATN, splenic avulsion and increased VTE risk. Peripheral neuropathies are rare. One case report of epistaxis due to vitamin K deficiency!

Results
Ketones in the urine
Hypochloremic alkalosis
Slightly elevated liver enzymes - amniotransferases elevations are 2-3 times normal, but can be 15-20 times normal. They should resolve
Electrolyte abnormalities, typically hypokalaemia
Transient hyperthyroidism


1st Line - Cyclizine
Antihistamines (Cyclizine) and phenothiazines should be prescribed.

2nd Line - Metoclopramide
Safe and effective but there is a risk of extrapyramidal side effects.

3rd Line - Ondansetron
Some mostly unproven link with ondansetron and septal defects.

Fluids
RCOG says no evidence any fluid is better than another.
Nausea apparently resolves faster with dextrose containing fluid, but you need to check the sodium and consider thiamime replacement first - with the dogma that otherwise you can precipitate Wernickes.

References and Links
http://bestbets.org/bets/bet.php?id=2923
http://pmj.bmj.com/content/postgradmedj/72/853/688.full.pdf
https://www.rcog.org.uk/globalassets/documents/guidelines/green-top-guidelines/gtg69-hyperemesis.pdf
https://wikem.org/wiki/Hyperemesis_gravidarum
http://pmj.bmj.com/content/78/916/76
http://bestpractice.bmj.com/best-practice/evidence/intervention/1405/0/sr-1405-i8.html

Tetanus

Wound Management 

In any patient with a wound, first do a risk assessment of the wound, and then their tetanus status:

Tetanus Prone Wound:  >6 hours old and needs surgical treatment
                                      Open compound fracture
                                      Contaminated puncture wound
                                      Clinical evidence of sepsis

High risk tetanus prone wound?   Yes - give immunoglobulin
                                    Heavy contamination with material likely to contain tetanus eg. manure
                                    Extensive devitalized tissue
                                    >24 hours since injury
                                    >10% burns

Tetanus Status Assessment 
Full immunisation - give immunoglobulin if very high risk
Partial immunization - give DTP if next dose due soon, if high risk give immunoglobulin
Not up to date  -give DTP.  Immunoglobulin
Uncertain - give DTP

Immunoglobulin
Give 500iu if it's a high risk tetanus wound
Give 250iu if it's a tetanus prone wound
Need a second dose of Ig if they can't have DTP, or if they have reduced capacity for antibody formation - radiotherapy, hypogammaglobulinaemia

Give both injections in different arms
If have a bleeding disorder, give SC. There is a higher risk of reaction when these are given SC rather than IM.

Tetanus
Tetanus is caused by C. tetani, a gram positive, anaerobic that is commonly found in soil and manure. It produces tetanospasmin, the neurotoxin that causes tetanus. Incubation 10 days. The infection is a  clinical diagnosis, defined as trismus with one or more of the following:
Spasticity
Dysphagia
Respiratory distress
Muscle spasms
Autonomic dysfunction

Treatment
Metronidazole - stop bacterial replication
Diazepam or midazolam - to control muscle spasms
Intravenous tetanus immunoglobulin -5,000 units < 50kg, 10,000 >  50kg. This is the same as the "treatment".
Intubation - may be needed. Sux is safe but there is a very high risk of autonomic instability
Wound cleansing and debridement

SAQ:
A forty eight year old patient attends the emergency department feeling unwell. They have an infected injection site in their anticubital fossa. They have severe trismus, and are writhing around with severe muscle spasms. Sister thinks security needs to escort them out. You suspect that they have a serious and rare infection from their injection site.

a) How would you manage the muscle spasms?
Supportive care with diazepam or midazolam.
b) How would you treat their infection?
You suspect tetanus - or you should because of the spasms. The patient needs supportive care, with monitoring and consideration of early intubation. Give metronidazole to prevent bacterial relocation. Give IM tetanus immunoglobulin 150 units/ kg. IV is no longer available. Monitor their renal function.
Wound debridement.
Watch for autonomic instability, and cardiac collapse. Sedation, and morphine to help reduce the amount of free catecholamine can be helpful.
c) How would you confirm infection?
Tetanus is a a clinical diagnosis.
You can look for serum levels, but these take so long for results to come back - don't delay treatment for serological confirmation.
- Tetanus IgG - If the antibody level is >0.1 IU/ml before IgG, this excludes current tetanus infection. - Detection of toxin in serum is a bio-assay and is only performed if the antibody level is below the protective threshold.
- Absence of toxin does not exclude tetanus.
- Detection of C. tetani in wound material or from a pure isolate

References
http://pedemmorsels.com/tetanus-prevention/
http://stemlynsblog.org/tetanus-in-the-ed/
https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/441356/IMW166.02_Tetanus_information_for_health_professionals_v1.4__2_.pdf
https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/441355/IMW165.02_Tetanus_Immunoglobulin_Handbook_v1.4.pdf
https://www.gov.uk/government/publications/tetanus-the-green-book-chapter-30
https://www.rcemlearning.co.uk/modules/tetanus/
https://www.rcemlearning.co.uk/foamed/september-2017/#1504201252016-ac52229b-9e50

Tumour Lysis Syndrome

https://lifeinthefastlane.com/ccc/tumour-lysis-syndrome/
http://bestpractice.bmj.com/best-practice/monograph/936/diagnosis/step-by-step.html
https://wikem.org/wiki/Tumor_lysis_syndrome
http://www.emdocs.net/9077-2/
http://dontforgetthebubbles.com/acute-lymphoblastic-leukaemia-day4/

Tumour lysis syndrome - probably something we've all seen in the ED, but never quite given a name. Is it important to give it a name - probably as it's a constellation of biochemical abnormalities that often requires intensive care treatment to correct...

What is it:
Cancer cells have got lots of electrolytes inside them. When they burst or lyse, normally due to chemotherapy, but maybe spontaneously, they release all these electrolytes into the circulation. Because in cancer there is a high cell mass turnover, this really causes problems.

Specifically:
- K+ up - rapid expulsion of intracellular K+ into circulation --> ventricular arrhythmias, weakness, paeasthesia, GI upset
- Tumour cells can have up to 4x normal levels of phosphate, so this is released by cell lysis. They need phosphate binders, and maybe dialysis.
The rapid increase in phosphate precipitates the calcium causing muscle cramps etc. Treat this with calcium only if they are symptomatic as there is a risk of precipitation with the phosphate.
- Release of purine nucleic acids into the circulation. Metabolised to uric acid --> renal failure. Allopurinol can help. No evidence for urine alkalisation.

It is more common in children and young adults with haematological malignancies, and normally happens at the beginning of their treatment. As we said, it can happen spontaneously but is normally 12 - 72 hours post chemo, and can be anything between -3 to 7 days before chemoterapy. It is most common in ALl, but can happen in other leukaemias, and poorly differentiated lymphoma like  burkitt lymphoma, high grade non- Hodkin). It can heppen in fast growing solid tumours. So unwell post chemo - might be neutropenic sepsis, but just have a think about the electrolytes.

All these electrolytes around cause renal failure is multifactorial but maybe due to volume depletion, cytokine mediated, precipitation of uric acid, calcium phosphate nephropathy.



Definition:
Cairo-Bishop Definition
Laboratory Tumour Lysis Syndrome:
Laboratory TLS is defined as an abnormality in 2 or more of the following, occurring within 3 days before or 7 days after chemotherapy:
Uric acid >476 micromol/L (8 mg/dL) or 25% increase
Potassium >6.0 mmol/L (6 mg/L) or 25% increase
Phosphate >2.1 mmol/L (6.5 mg/dL) in children or >1.45 mmol/L in adults (4.5 mg/dL) or 25% increase
Calcium <1.75 mmol/L (7 mg/dL) or 25% decrease from baseline.

Clinical
Laboratory syndrome + creatinie >1.5times upper age limit, cardiac dysrhythmia, seizure

Presentation
Presents with GI upset fluid overload, haematuria, symptoms of metabolic derrangements

Look for signs of metabolic derrangement
- arrhythmias, weakness, paraesthesia, tetany, renal failure

Investigate
All the electrolytes
- K+ high, phosphate +, calcium low, urea up, low bicarb, high LDH

Management
Prevention - allopurinol (inhibition of xanthine oxidase can last 18-30hours. Acts slowly so is more prevention), pre chemo hydration
 aggressive hydration, maybe with diuretics. Aim for 3L urine output in 24hours.
 metabolic correction
 support of renal failure

Rasburicase – a medication that converts uric acid to allantoin which is water soluble and excreted in the urine.

Often need ICU care for electrolyte correction

Further Reading
https://lifeinthefastlane.com/oncology-quandary-002/
https://emsimcases.com/2016/09/13/tumour-lysis-syndrome/ for a

Cerebral Venous Thrombosis

In a lot of places I work, headaches either go home for GP review, or get admitted as a ?SAH. And if they're a possible SAHs, they get a normal CT in six hours (maybe) and many go home without an LP. This really worries me, as there's loads of other serious causes of headache I don't think we exclude thoroughly. In the "old" days, a second doctor generally reviewed the ?SAH to do (or get the results of) a lumbar puncture. So one of the diagnoses we could be missing that worries me is a cerebral  venous thrombosis - this is dangerous to miss.


 Is there a difference between cerebral venous thrombosis and cavernous venous sinus thrombosis?
CVT and CVST have common underlying etiologies including thrombosis, and terms are occasionally used synonomously. CVST is specifically thrombosis in the cavernous sinus, normally with infection, so cerebral venous thrombosis is a safer term.

Pathology
If you can't remember your venous sinus anatomy, check out Andy's posts on emergency medicine ireland. I can not think of a better way to learn anatomy.
At a very basic level, what happens is you get a clot in one of the veins in the head, which causes problems. At its worst, this can cause death and coma. Middling effects present as a stroke, especially now anyone slightly lopsided seems to get a stroke call. At the "mild" end, a headache may be the only presenting symptom.

There are lots of theories about what is happening to cause these symptoms. It is thought that venous occlusion leads to the development of collateral veins, which combined with altered arachnoid absorption of CSF causes cerebral oedema - which can cause the headache. They can also cause cerebral venous infarction (in 50% of cases) and even haemorrhage.


Risk Factors
Excess Oestrogen: 
oral contraceptive pill: very common cause in female patients <50 years of age 2
pregnancy, IVF
puerperium - more common then than in the pregnancy

Clotty 
prothrombotic haematological conditions: 35% 2
e.g. prothrombin 20210 (factor II) mutation 7
infection: especially mastoid sinus (dural sinus occlusive disease - DSOD)
systemic illness
dehydration: e.g. gastroenteritis
sepsis
malignancy
connective tissue disorders

Local Factors
skull abnormalities/trauma
compressing mass: e.g. meningioma

steroids
idiopathic: ~12% - this is worrying. If you're going to get a rare disease, being in the rarest bit of rare is unlucky!

Presenting Features
Headache (70-90% of cases)
    There is no particular "type" of headache, but it is normally persistent. Onset may be sudden, like in sub-arachnoid, or gradual. Most patients present with symptoms that have evolved over days or weeks.
Headache is the most frequently (80–90%) occurring symptom in cerebral venous thrombosis and often the first symptom reported by patients. The International Classification of Headache Disorders describes the headache as having no specific characteristics[2] but one study found the headache was usually acute or subacute in onset, localised, continuous and moderate to severe.[23] Cases have been reported where headache is the only neurological symptom or sign but this is very rare.

"Stroke"
  Stroke without any typical risk factors, especially in young people may be due to CVT. Up to 75% of cases have focal deficit and headache.
Diplopia here (CN VI palsy) is a focal sign here, and should stimulate you to look for papiloedema...and really think hard about CVT.

Symptoms are not always classic, but they can be associated with the thrombus location.3,4
– Cortical vein thrombosis presents with motor and sensory deficits, as well as seizure.
– Sagittal sinus thrombosis may present with motor deficits, bilateral deficits, and seizures.
– Patients with thrombus in the lateral sinus may present with intracranial hypertension and headache alone.
– Thrombosis of the left transverse sinus can present as aphasia.
– Thrombosis of the deep venous sinus can cause behavioral symptoms due to lesions in the thalamus.

Cavernous sinus thrombosis is associated with ocular pain, chemosis, proptosis, and oculomotor palsies.3,4


 Seizures
 Seizures occur in 30- 50% of presentations, and they are often followed by a Todd's paresis. Superior sagittal sinus thrombosis (4%) can present with bilateral or alternating neurological deficits.

 Coma or encephalopathy
This isn't common, but you can get a rapidly progressive illness with deepening coma, headache, nausea and pyramidal signs, due to extensive involvement of the deep cerebral veins.
More often other clinical manifestations present at onset or develop during the course of the disease. These include papilloedema, focal deficits, altered consciousness, seizures and cranial nerve signs, in particular diplopia caused by sixth nerve palsy. Psychosis, in conjunction with focal neurological signs, has also been reported.[25] The development of symptoms may occur over hours, days or even weeks.

Examination Features
 Papilloedema
 Altered vision
 Neurological symptoms

Investigations
Examination of the cerebrospinal fluid (CSF) does not necessarily help in establishing the diagnosis as there are no pathognomonic features. Abnormalities are found in up to 84% of cases and include raised CSF pressure, increased protein content, the presence of red blood cells and pleocytosis.
D-dimers probably not useful

Radiology 
CT -             Often normal, but there may be subtle hyperdensity of the affected sinus or vein for the first 7 - 14 days. May have associated venous haemorrhage or infarction. Haemorrhagic infarcts may be multiple, in no particular location.

String Sign
Seen in 25% of patients with a cavernous sinus thrombosis. It looks like elongated hyperdense image relating to the brain parenchyma.

Dense Triangle
This can be seen in the first two weeks in up to 60% of patients. Fresh, coagulated blood causes a superior sagittal sinus opacification. The opposite of this is the empty delta sign, where contrast is administered highlighting an intraluminal filling deficit. It is not a specific sign.


Treatment
Anticoagulation - In the last Confidential Enquiries into Maternal Deaths in the United Kingdom report there were four deaths from CVT compared with eight in 2003–05.[22] The previous report expressed the hope that increasing application of thromboprophylaxis among at-risk women will reduce deaths from both pulmonary embolism and CVT but figures are as yet too small to draw a conclusion.[1]

General measures like proper headboard inclination, adequate oxygenation, and protection of airway due to risk of bronchoaspiration are recommended (although now this has been disproved in stroke, I wonder if its accurate).
Anti-convulsant treatment after even a single seizure is reasonable

Lumbar puncture not recommended by LITFL

Full References 
http://onlinelibrary.wiley.com/doi/10.1111/tog.12101/full
http://onlinelibrary.wiley.com/doi/10.1111/tog.12101/abstract
https://lifeinthefastlane.com/ccc/cerebral-venous-thrombosis/
http://pmj.bmj.com/content/76/891/12
http://www.emdocs.net/cerebral-venous-thrombosis-pearls-and-pitfalls/
http://emedicine.medscape.com/article/1162804-overview#a7
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3858762/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4517419/
http://emergencymedicineireland.com/2012/03/anatomy-for-emergency-medicine-8-cerebral-venous-sinuses/
https://radiopaedia.org/articles/cerebral-venous-thrombosis
https://emin5.com/2017/02/22/approach-to-headaches/
https://stmungos-ed.com/s/N8.pdf