ANSWERS
CASE 8: A YOUNG WOMAN IS FOUND UNCONSCIOUS IN BED
A 27-year-old woman is brought into the emergency department by her husband, who found her unconscious in bed. The paramedics perform an ABCDE assessment and find her finger- prick glucose to be 1.2 mM. Administration of 50 mL of 20% dextrose revives her. In hospi
tal, the patient gives a history of awakening that morning with a headache but not being able to remember anything else. She has no past medical history, and family history is positive for ‘thyroid problems’ in her mother. She is a non-smoker and drinks alcohol only socially, though she does confess to drinking large amounts of Coca-Cola every day.
Examination
Cardiac, respiratory, abdominal and neurologic examinations are all unremarkable.
INVESTIGATIONS
FBC, U+E Normal
Random glucose 5.5 mM
Thyroid-stimulating hormone 2 mU/L
Short Synacthen test Within normal limits
Given the history of a hypoglycaemic episode, a supervised fast is performed. At the start of the fast (8 am), plasma glucose is 5.4 mM, falling to 4.2 mM at noon, and then 2.3 mM at 4 pm, before reaching a nadir of 1.8 mM at 6 pm. At that time the fast is stopped, and levels of insulin and C-peptide taken at this point are 70 pM (5–20) and 25 nM (0.2–0.9), respectively.
QUESTIONS
1. What are the causes of the patient’s hypoglycaemic state?
2. Explain the rationale for the investigations performed in this case. Why would the physician feel confident of a diagnosis at the end of these?
3. What further tests are required at this stage with regard to forming a manage
ment plan for the patient?
4. What are the principles of treatment in this case, and how should the patient be treated while awaiting her definitive management?
5. What follow-up should the patient receive?
DOI: 10.1201/9781003242697-9
100 Cases in Clinical Pathology and Laboratory Medicine 20
ANSWERS
Blood glucose level is determined by the balance between insulin and the counter-regulatory hormones (glucagon, adrenaline, growth hormone and cortisol), with hypoglycaemia arising when the balance is shifted too far towards the latter. The clinical features of hypoglycaemia are divided into either autonomic or neurologic symptoms. This presentation highlights the neuroglycopaenic symptoms (e.g., blurred vision, amnesia, loss of consciousness) that occur as a result of a deficient supply of glucose to the brain. The responses of glucagon and adrenaline to a low-glucose state are responsible for the symptoms of autonomic hyper-reactivity, such as sweating, tremor, nausea and palpitations.
Symptomatic hypoglycaemia has several causes, which may be broadly classified as either fasting or non-fasting. Non-fasting hypoglycaemia occurs after a meal; possible causes of this include (1) gastrectomy or alimentary bypass surgery resulting in rapid gastric empty
ing, leading to overproduction of insulin; (2) pancreatic islet cell hyperplasia; and (3) occult diabetes, which may produce late hypoglycaemia after a meal owing to the deficient early response of insulin in diabetics, leading to exaggerated delayed release 4–5 hours afterwards.
The causes of fasting hypoglycaemia include:
1. Hyperinsulinaemic states
a. Insulin reaction or sulphonylurea overdose (the most common cause) b. Autoimmune hypoglycaemia
c. Surreptitious use of insulin or sulphonylureas d. Pancreatic β-cell tumours (typically insulinoma) 2. Non-hyperinsulinaemic states
a. Reduced hepatic gluconeogenesis, which may arise from liver disease or inborn errors of metabolism
b. Renal insufficiency (the kidney contributes to gluconeogenesis too)
c. Alcohol excess, which increases the activity of alcohol dehydrogenase (consum
ing NAD+) and thereby limits the conversion of lactate to pyruvate, which is a gluconeogenic substrate
d. Non-pancreatic tumours (e.g., retroperitoneal fibrosarcoma) that release insulin-like growth factor (IGF)-2, which can activate the insulin receptor
This patient has fasting hypoglycaemia (a clue is the persistent drinking of Coca-Cola as a subconscious defence against this), and the absence of other causes point towards a hyper
insulinaemic state as the cause. If we assume that the patient has not been using insulin or other antidiabetic agents, the most important diagnosis to exclude is an insulinoma, which is the most common cause of spontaneous, fasting hypoglycaemia in an otherwise healthy individual.
Insulinomas are benign tumours of pancreatic β-cells, with hypoglycaemia arising from excess secretion of insulin. The key investigation for insulinoma is a supervised fast, the premise of which is to elicit Whipple’s triad, which is required for diagnosis. Whipple’s triad requires (1) symptoms to be associated with fasting or exercise, (2) confirmation of hypogly
caemia during these episodes and (3) reversal of symptoms on administering glucose. In this case, all three criteria are met, and the inappropriately high levels of insulin at the end of the fast (with a glucose level of 1.8 mM) confirm hyperinsulinism. The high C-peptide levels confirm an endogenous rather than exogenous cause (C-peptide is the other product from cleavage of pro-insulin and is released with insulin from β-cells).
Case 8: A Young Woman Is Found Unconscious in Bed 21
As the majority of insulinomas are single and benign, the treatment of choice is surgical resection. Further investigations are needed for tumour localisation, including abdominal ultrasound and CT; endoscopic ultrasound may be useful to identify pancreatic lesions. If these are not fruitful, selective angiography of pancreatic vessels with calcium stimulation (to cause vesicle release) and measurement of insulin levels in the hepatic vein may help locate the tumour anatomically.
While awaiting surgery, options to manage the hypoglycaemia include cornstarch infusion at night (this releases glucose in a slow, sustained fashion) and diazoxide, a thiazide-type drug that opens the KATP channel, leading to efflux of K+ from β-cells, which causes hyperpolari
sation and reduced insulin release.
The finding of an insulinoma in a young patient should raise the possibility of an endocrine syndrome, in particular multiple endocrine neoplasia type 1 (MEN1). This is an autosomal dominant syndrome characterised by tumours in the pancreas, pituitary and parathyroids (‘3Ps’) caused by germline mutations in the MEN1 gene. While insulinoma is generally not a presenting feature of MEN1, the family history of ‘thyroid problems’ should serve to raise notice about its relevance to this patient.
KEY POINTS
• The symptoms of hypoglycaemia arise from neuroglycopenia and autonomic hyper-reactivity.
• The most common cause of fasting hypoglycaemia in an otherwise healthy person is an insulinoma.
• The diagnosis of insulinoma is made by fulfilling Whipple’s triad.
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