Hypoadrenalism (inc Addison's) Flashcards
Addison’s Disease
Addison’s disease
Autoimmune destruction of the adrenal glands is the commonest cause of primary hypoadrenalism in the UK, accounting for 80% of cases
Features
lethargy, weakness, anorexia, nausea & vomiting, weight loss, ‘salt-craving’
hyperpigmentation (especially palmar creases), vitiligo, loss of pubic hair in women, hypotension
crisis: collapse, shock, pyrexia
Mx = STEROIDS
Other Causes of Hypoadrenalism
Other causes of hypoadrenalism
Primary causes tuberculosis metastases (e.g. bronchial carcinoma) meningococcal septicaemia (Waterhouse-Friderichsen syndrome) HIV antiphospholipid syndrome
Secondary causes pituitary disorders (e.g. tumours, irradiation, infiltration)
Exogenous glucocorticoid therapy
Adrenal Failure in Developing World - Example Question
A 56-year-old Kenyan female has a 6 month history of weight loss of 5 kg associated with episodic severe colicky abdominal pain not associated with eating or bowel opening.
Na+ 126 mmol/l K+ 6.5 mmol/l Urea 14.3 mmol/l Creatinine 157 µmol/l Glucose 3.2 mmol/l T4 7.5 pmol/L (NR 9-20 pmol/L) TSH 11.2 mIU/L (NR 0.3-6.0 mIU/L)
Thyroid antibodies are not detected.
What is the most likely diagnosis?
Hypopituitarism MEN type 1 Autoimmune adrenal failure Primary hypothyroidism > Adrenal failure secondary to TB
This patient has adrenal failure (hyponatraemia, hyperkalaemia, raised urea and creatinine, hypoglycaemia). Addison’s disease in the western world is mostly due to autoimmune causes (associated with adrenal auto-antibodies and anti-thyroid antibodies) however in the developing world TB is the most common cause.
Diagnosis is confirmed with the synacthen test (deliver tetracosactrin followed by measuring serum cortisol at 0, 30, 60 minutes later - a normal result is an increase in cortisol to >250nmol/L at 30mins and >550nmol/L by 60mins). The normal response is a rise in cortisol level; in adrenal insufficiency this does not occur.
ACTH levels are also raised in primary adrenal failure and abdominal X ray may show adrenal calcification from TB.
Treatment is with hydrocortisone 20-30mg a day with fludrocortisone 0.1mg if hypotensive.
The low T4 may indicate hypothyroidism but the raised TSH excludes hypopituitarism. A low T4 is seen in Addison’s disease in the absence of functional hypothyroidism, and corrects with steroid replacement.
Addisonian Crisis - Example Question
A 20-year-old female presented to the accident and emergency department with severe abdominal pain, vomiting and lethargy. On further questioning she stated that she had been generally unwell for the last four months during which time she lost 10 Kg in weight and had been tired all the time.
Last month she has been diagnosed with hypothyroidism and was prescribed levothyroxine 50 mcg daily.
Her mother and sister have hypothyroidism and take thyroxine. On examination, she looks unwell and dehydrated.
Her pulse is 105 beats per minute and blood pressure is 70/40 mmHg
Her temperature is 37.6ºC and BMI is 19 kg/m². Cardiovascular, respiratory and abdominal examination were normal. Investigations done last month showed:
Hb 9.5 g/dl
MCV 105 fl
Platelets 190 * 109/l
WBC 4.5 * 109/l
Serum free T4 8.5 pmol/l
Serum TSH 5.5 mU/l
While awaiting new investigations, what is the most appropriate immediate treatment for this patient?
Intravenous glucose 10% Intravenous normal saline Intravenous normal saline and antibiotics > Intravenous normal saline and hydrocortisone Intravenous thyroxine
This patient presented with Addisonian crisis (abdominal pain, vomiting, dehydration and hypotension). She has been complaining of tiredness and weight loss (which are features of Addisons disease) for four months but what precipitated the crisis is the thyroxine given for the presumed hypothyroidism.
Actually, a slightly raised TSH and a decreased T4 are features of primary hypoadrenalism and do not necessarily indicate frank hypothyroidism.
This is a medical emergency and should be treated immediately with intravenous normal saline and hydrocortisone. Thyroxine should not be given as it will exacerbate the condition.
Her low haemoglobin and high MCV may point towards pernicious anaemia which is an autoimmune disease seen sometimes in association with Addisons disease.
Addisonian Crisis
Addisonian crisis
Causes
sepsis or surgery causing an acute exacerbation of chronic insufficiency (Addison’s, Hypopituitarism)
adrenal haemorrhage eg Waterhouse-Friderichsen syndrome (fulminant meningococcemia)
steroid withdrawal
Management
hydrocortisone 100 mg im or iv
1 litre normal saline infused over 30-60 mins or with dextrose if hypoglycaemic
continue hydrocortisone 6 hourly until the patient is stable. No fludrocortisone is required because high cortisol exerts weak mineralocorticoid action
oral replacement may begin after 24 hours and be reduced to maintenance over 3-4 days
Primary Adrenal Insufficiency Crisis: Example Question
A 33-year-old female is brought into the emergency department as a stand-by. She has felt unwell for the past 2 weeks. She describes lethargy, light-headedness and occasional shortness of breath. More recently she developed urinary frequency and dysuria. She received a domiciliary visit from her general practitioner 2 days ago and was prescribed trimethoprim for a possible urinary tract infection.
On arrival, she appears pale and clammy. Her peripheries are cold. Her observations reveal oxygen saturations of 94% on air, respiratory rate 28/min, heart rate 117/min, blood pressure 65/30 mmHg.
She has a past medical history of type 1 diabetes, uterine fibroids and hypothyroidism.
Initial investigations reveal:
White cell count 17.8 *109/l Haemoglobin 97 g/l Mean cell volume (MCV) 103.7 fL Sodium 134 mmol/l Potassium 4.9 mmol/l Urea 7.0 mmol/l Creatinine 120 µmol/l Bilirubin 45 µmol/l Alanine transaminase (ALT) 1051 U/l Albumin 16 g/l C-reactive protein (CRP) 71 mg/dL Glucose 9.1 mmol/l
Urinalysis: ++protein, ++blood, +++leukocytes, ++nitrites, trace ketones
She is given intravenous fluids. Her blood pressure is 82/45 mmHg after a total of 3 litres of fluids. She is started on intravenous amoxicillin and gentamicin.
What is the next step in her management?
1000mls intravenous colloid fluid > Intravenous hydrocortisone Intravenous noradrenaline Intravenous albumin Intravenous meropenem
This patient has an autoimmune diathesis: she has type 1 diabetes and hypothyroidism. Her macrocytic anaemia also raises the possibility of undiagnosed pernicious anaemia. She is therefore at very high risk of primary adrenal insufficiency (Addison’s Disease). IV hydrocortisone is a potentially life-saving treatment and should be given immediately. It is not contra-indicated in the presence of sepsis. Her biochemistry is not classical for Addison’s, however, this does not exclude the diagnosis. Her abnormal LFTs are in keeping with a shocked liver. Intensive care review should be sought and she may well require inotropes but treatment of potential adrenal insufficiency is the immediate priority.
Addisonian Crisis - Example Question
A 19-year-old woman with a history of type 1 diabetes is brought to the Emergency department with nausea and vomiting. there is no history of diarrhoea. She also has coeliac disease. She follows a gluten free diet and takes a basal bolus insulin regime with a usual HbA1c of 53 mmol/mol. On examination her blood pressure is 100/80 mmHg with a postural drop of 20 mmHg. Pulse is 88 beats per minute and regular. She looks dehydrated and tanned, she puts her tan down to weeks in the garden after her exams.
Investigations
Hb 102 g/l Na+ 129 mmol/l Platelets 189 * 109/l K+ 5.0 mmol/l WBC 10.9 * 109/l Urea 9.9 mmol/l Neuts 6.2 * 109/l Creatinine 113 µmol/l Lymphs 1.1 * 109/l CRP 42 mg/l Eosin 1.5 * 109/l
Which of the following is the most important intervention with respect to her management?
Fluid restriction IV anti-emetic > IV hydrocortisone IV normal saline NG feeding
In a patient with type 1 diabetes, such tight glycaemic control with hypoglycaemia would be considered very unusual. Coupled with the easy tanning, nausea, vomiting, and postural drop in blood pressure, this is highly suggestive of possible Addison’s disease. The slight rise in eosinophil count, anaemia, hyponatraemia and potassium at the upper end of the normal range, all support the diagnosis.
In this situation corticosteroid replacement is crucial, without it normal saline replacement alone won’t correct any hypotension, nor will it improve hyponatraemia. Although anti-emetics and NG feeding may be useful in restoring this patient to health, they won’t correct underlying adrenal insufficiency.
Addisonian Crisis - Example Question
A 24 year old female patient attends the young persons diabetes clinic for a routine follow up. She developed type 1 diabetes mellitus 4 years ago, presenting in DKA at that time. Since then she has been well controlled on carbohydrate counting and basal bolus insulin. Since starting treatment with insulin she has developed vitiligo on her hands and feet which causes her some distress. She is very aware of her skin pigmentation due to her vitiligo and reports on this encounter that she feels her skin in her armpits has gotten darker. She also reports vague symptoms of nausea, weight loss and muscle weakness. She has had to stop playing badminton with her friends due to occasional light-headedness and having fainted once. Her blood sugar diary shows an early morning (fasting) level of 7.1. The highest sugar level recorded is 13.2 with the occasional dip below 4.0.
Examination reveals hyperpigmentation of the axilla bilaterally. There is vitiligo present in both hands and feet but this is consistent with previous examinations. Abdominal examination reveals generalised tenderness with no guarding, some abdominal striae are seen.
Some simple investigations are carried out
Blood Pressure
Lying - 110/76mmHg
Standing 1 minute 94/70mmHg
Standing 3 minutes 86/66mmHg
Hb 12.0 g/dl
Platelets 321 * 109/l
WBC 5.3 * 109/l
Na+ 128 mmol/l K+ 5.6 mmol/l Urea 5.6 mmol/l Creatinine 82 µmol/l Bicarbonate 16mmol/l Random glucose 4.1 mmol/l HBA1c 58mmol/mol (7.5%)
Given the most likely diagnosis, what is the most important immediate management?
IV Hypertonic (3%) saline IV 0.45% Saline + 5% Dextrose Oral Glucose drink IV Bicarbonate (1.24%) Infusion > 100mg IV hydrocortisone
The symptoms and findings above are highly suggestive of Addison’s Disease with the early signs of Addisonian Crises. The immediate management is to give steroids to replace the deficiency that is present. The patient above will also need adequate rehydration therapy. Once steroids are given they may be able to take this orally, but in reality most patients would be started on intravenous 0.9% saline. The results shown above do not suggest the presence of hypoglycaemia and after the injection of steroids this blood sugar level is likely to increase.
In this instance the Addison’s Disease is part of the autoimmune polyendocrine syndrome type 2 (also known as Schmidt’s Syndrome). In a patient presenting with more than one endocrine or autoimmune disorder there should be some consideration of other possible disorders. Some would advocate the testing for antibodies to 21-hydroxylase (a feature of Addison’s disease) to try and pre-empt the development of that condition and to allow for treatment before a dangerous crisis occurs.
Addisonian Crisis: Example Question
A 24-year-old lady presents to hospital with increasing confusion. Her parents describe a gradual history of weight loss, lethargy with abdominal cramping. She has no past medical history and is prescribed no regular medications. She lives with her parents. Her mother suffers from hypothyroidism and her father from hypertension which is controlled with bendroflumethiazide.
On examination she is thin, with cool skin and sunken eyes. Her capillary refill time is 3 seconds with dry mucous membranes. Auscultation of her chest reveals bilateral symmetrical vesicular breath sounds. Her abdomen is soft with normal bowel sounds. She is confused with a Glasgow Coma Scale of 14. She has no focal neurology.
Her investigations reveal;
Hb 10.4 g/dL
MCV 90 fL
WCC 6.4 *10^9/l
Platelets 170 *10^9/l
Na+ 105 mmol/L K+ 5.8 mmol/L Ur 8.8 mmol/L Cr 90 µmol/L Glucose 3.9 mmol/L
Urinary Osmolality 108 mmol/L
Urinary Sodium 67 mmol/L
Chest X ray Clear
CT Head No intracranial abnormalities
What is the most likely diagnosis?
> Adrenal insufficiency Laxative abuse Hypothyroidism Diuretic use SiADH
This lady has hypovolaemic hyponatraemia. Sodium can be lost through the gastrointestinal tract, skin or urinary tract. This patient is likely to have renal loss secondary to adrenal insufficiency.
The urinary sodium would be reduced if there were gastrointestinal or skin losses. Also, the patient would be hypokalaemic if there were laxative abuse. The patient would be expected to have hypokalaemia if there were abuse of bendrofumethiazide.
The patient is hypovolaemic and therefore SiADH is excluded, also, hypothyroidism and adrenal insufficiency have not been excluded which would be necessary to make the diagnosis of SiADH.
Hypothyroidism classically presents with weight gain and euvolaemic hyponatraemia.
This patient has adrenal insufficiency. It is possibly of an autoimmune nature with a probable autoimmune hypothyroidism in the immediate family. She has a gradual onset of non-specific symptoms lethargy, weight loss and abdominal symptoms. The hyponatraemia has caused confusion. The blood tests reveal hypoglycaemia, hyponatraemia with hyperkalaemia and normocytic anaemia. Examination revealed signs of hypovolaemia, it also could show skin or mucus membrane pigmentation.
Addison’s - Example Question
A 22-year-old female, who is known to have type 1 diabetes mellitus, presents with weight loss, anorexia and fatigue for the last six months.
Her diabetes was well controlled with soluble insulin three times daily and long acting insulin in the evening but during the last six months she noticed that her insulin requirement has generally decreased and on three occasions she had hypoglycaemic attacks.
During the same time period she had lost approximately 7 Kg in weight and had generally lost her appetite. She had also been amenorrhoeic over the last three months.
On examination, she is thin (BMI 18), with a pulse rate of 70 beats per minute and a blood pressure of 110/70 mmHg with a postural drop.
Investigations reveal:
Serum sodium 125mmol/L Serum potassium 5.3mmol/L Serum urea 7.4mmol/L Serum creatinine 100 mol/L Serum glucose 7.5mmol/L HbA1c 6.0% Serum free T4 7.5 pmol/L Serum TSH 5.5 pmol/L Serum oestradiol 70 pmol/L (130-850) Serum LH 2.5 mU/L (2-10) Serum FSH 2.2 mU/L (2-10) Serum prolactin 400 mU/L (50-450) Serum calcium 2.9 mmol/l Serum phosphate 0.8 mmol/l
What is the most appropriate investigation for this patient?
Thyroid autoantibodies PTH concentration > Short synacthen test Pregnancy test Random cortisol concentration
This known type 1 diabetic female has developed Addisons disease on top of her diabetes. This explains the hypoglycaemic attacks, the decrease in her insulin requirement, the fatigue and weight loss.
Both type 1 DM and Addisons disease are features of Schmidt’s disease (type 2 autoimmune polyendocrine syndrome) which is the diagnosis in this case.
The low T4, raised TSH, high calcium, low FSH, low LH, low oestradiol (hypogonadotrophic hypogonadism) are all features of Addisons disease.
The best investigation to diagnose Addisons disease is the short synacthen test.
It is of paramount importance when treating these patients is not to replace thyroxine before hydrocortisone because this will induce Addisonian crisis.
Adrenal Insufficiency in HIV - Example Question
A 55-year-old man was seen in the Emergency Department after a fainting episode. He describes a history of fatigue and nausea. His past medical history includes type 2 diabetes mellitus and HIV infection and he admits that he has not been compliant with any medications, including his anti-retroviral therapy.
On examination, his pulse was 65 beats per minute and regular, blood pressure 90/62 mmHg and respiratory rate 26 breaths per minute.
Investigations:
Haemoglobin 14.0 g/dL (13.0-18.0) White cell count 4 x 10^9/L (4-11) Platelets 150 x 10^9/L (150-400) Sodium 130 mmol/L (135-145) Potassium 5.8 mmol/L (3.5-5.0) Creatinine 80µmol/L (60-110) Glucose 4.0 mmol/L (4.0-7.8)
What is the most appropriate next step management step?
Salbutamol nebuliser Broad-spectrum antibiotics Sliding scale insulin infusion > Intravenous hydrocortisone Restart anti-retroviral medications
Adrenal insufficiency affects approximately 10% of patients with HIV, commonly due to cytomegalovirus (CMV)-related necrotising adrenalitis. It is the failure of the adaptive immune system seen in HIV infection, and particularly AIDS, that increases susceptibility to CMV infection, and thus risk of CMV-associated adrenal failure.
The immediate management of hypoadrenalism involves rapid steroid replacement; fluid resuscitation would also be a priority.
There is no firm evidence here to suggest bacterial infection, and the hyperkalaemia should resolve with appropriate management of the hypoadrenalism.
Long term steroid use and Hypoadrenalism - Example Question
A 53 year old female presents with 48 hours of general malaise. 30 years ago, she underwent a resection of a pituitary mass and has since been complaint on desmopressin, levothyroxine and hydrocortisone, up until her last dose earlier in the morning. She has no other past medical history. Her husband reports the patient to have had reduced oral intake for the past 2 days while she has been unwell. She has no reported head injuries, rigors or pyrexia. On examination, her GCS is E3 V2 M5. She is cool peripherally and a temperature demonstrates 33.4 degrees under her tongue. Her spot blood glucose is 2.2 mmol/l. Her blood pressure is 86/50 HR 110 and sinus rhythm. Blood tests demonstrate Na 158, K 4.2. What is your first action(s)?
Send thyroid function test Administer IV liothyronine Send random cortisol > Administer IV hydrocortisone CT head, blood culture, urine dip, HbA1c
In the context of a sudden decline in any patient with long-term steroid use with hypotension, hypothermia and hypoglycaemia, you must treat presumptively for Addisonian crisis. It must be remembered while the classic biochemical presentation of hyponatraemia and hyperkaelamia is frequently quoted in textbooks, this is frequently not the case in real life. While she may indeed be thyroid deficient, neither thyroid function tests nor intravenous free T3 is the most immediate treatment. A random cortisol, in the context of recent hydrocortisone in the community, is uninterpretable.
Long term steroid use - Mx during infection: Example Question
A 71-year-old man presents to the emergency department having collapsed at home. On admission, he is confused and his daughter, who accompanied him to the emergency department states that she found him on the floor of the bathroom. There had not been any urinary incontinence or signs that he had bitten his tongue. He had been feeling hot and complaining of pain on urinating several days before the collapse. His past medical history includes rheumatoid arthritis, for which he takes long-term oral steroids. He is diagnosed in the emergency department as having urosepsis and is commenced on intravenous fluids and antibiotics.
What is the most appropriate other treatment for this patient?
> IV hydrocortisone IV hydrocortisone and fludrocortisone Oral prednisolone and fludrocortisone IV methylprednisolone and fludrocortisone Oral prednisolone
This patient is on long-term oral steroids for his rheumatoid arthritis and has urosepsis. His requirements for steroids will be higher due to his current illness, thus he should be given steroids as soon as possible. Intravenous hydrocortisone is the most appropriate treatment to add in.
Addison’s - Investigations
Addison’s disease: investigations
In a patient with suspected Addison’s disease the definite investigation is a ACTH stimulation test (short Synacthen test). Plasma cortisol is measured before and 30 minutes after giving Synacthen 250ug IM. Adrenal autoantibodies such as anti-21-hydroxylase may also be demonstrated.
If a ACTH stimulation test is not readily available (e.g. in primary care) then sending a 9 am serum cortisol can be useful:
> 500 nmol/l makes Addison’s very unlikely
< 100 nmol/l is definitely abnormal
100-500 nmol/l should prompt a ACTH stimulation test to be performed
Associated electrolyte abnormalities are seen in around one-third of undiagnosed patients: hyperkalaemia hyponatraemia hypoglycaemia metabolic acidosis
Addison’s - Hidden Diagnosis - Example Question
A 28 year old lady has noticed over the last year that she does not tollerate cold weather well. She is fatigued and her partner notices that she is also low in mood despite having no obvious triggers. Physical examination is unremarkable. Her electrocardiogram (ECG) demonstrates a sinus rhythm at 43 beats per minute. She has a background of type 1 diabetes mellitus for which she takes insulin. She also has coeliac disease. Her blood results are shown below:
Hb 136 g/dl
MCV 103 fL
Na 133 mmol/l
K 4 mmol/l
Urea 3.5 mmol/l
Creatinine 70 µmol/l
Glycosylated haemoglobin (HbA1c) 51 mmol/mol (6.8%) TSH 9.2 mIU/L (reference range 0.3-4.0 mIU/L T3 2 pmol/L (reference range 3-9 pmol/L) T4 5 pmol/L (reference range 9-25 pmol/L)
What is the next best step in her management?
Commence levothyroxine Commence carbimazole Ultrasound scan thyroid MRI pituitary > Short synacthen test
Every time you see type 1 diabetes, pernicious anaemia, rheumatoid arthritis, coeliac, or indeed ANY of the autoimmune conditions in the past medical history of a patient in the exam engage autoimmune mode in your brain. Once you have done that, you will be specifically looking not to miss other coexistent autoimmune conditions they may be trying to hide from you behind a cryptic clinical sign or some subtle blood abnormality. In this example, where she has type 1 diabetes, thinking like that then gives you the diagnosis of an autoimmune hypothyroid cause (Hashimoto's). If you think you have made a diagnosis of Hashimoto’s, you should routinely next always look to rule out Addison’s, even if the sodium is normal (which it isn’t in this example: a subtle blood abnormality). Addison’s (just like other autoimmune conditions) may coexist with Hashimoto’s. However, the danger with missing Addison’s in Hashimoto’s is that it sits there masked by the hypothyroid. If you miss it and treat the hypothyroid blindly first without covering the Addison’s, you will unmask the Addison’s and the patient will come back in an adrenal crisis a few days later.
