Case history 33

James is 5 years old and is much smaller than his classmates at school. His growth rate has been
monitored and has clearly dropped off markedly in the past year. He is an active child, and on
examination has normal body proportions. His mother and father are of average height. His bone age
is that of a 3-year-old child. 
What biochemical tests would be appropriate in the investigation of this boy?
* Growth hormone deficiency should be suspected particularly in view of the documented fall-off in
the patient’s growth rate over the previous year. Random GH measurement is potentially misleading –
false-positive and false-negative results are frequent. Many endocrinologists measure stimulated GH;
a result >6 µg/L excludes GH deficiency.

Case history 34
A 49-year-old woman receiving hormone replacement therapy was found to have a thyroid nodule. No
lymphadenopathy was detectable and clinically she appeared to be euthyroid. A technetium scan
revealed a ‘cold’ nodule and an ultrasound scan indicated it was cystic. Biochemistry results in a
serum specimen:
T4 TSH
(nmol/L) (mU/L)
172 0.40
Explain why the T4 is elevated.
What other investigations should be performed in this patient?
* This patient has a high serum T4 because the oestrogen component of hormone replacement therapy
stimulates the synthesis of thyroxine-binding globulin. Thus, to maintain a normal level of the
physiologically active free T4 the total serum T4 needs to be increased. The measured free T4 is likely
to be within reference limits. By far the most important investigation for this woman is a fine-needle
aspiration biopsy of the thyroid nodule. Frequently, cystic lesions will be drained by this procedure
and may not recur. It is important, however, that adequate thyroid epithelium be obtained to enable
the diagnosis of thyroid cancer to be excluded or confirmed.

Case history 35
Investigation of a 63-year-old woman with effort angina revealed a serum TSH of 96 mU/L and a
serum free T4 of 3.7 pmol/L. An ECG showed some evidence of ischaemia but was not diagnostic of
myocardial infarction. Further biochemical investigation revealed:
Cholesterol Creatine kinase AST
(mmol/L) (U/L)
9.3 450 70
How should these results be interpreted?
* The low free T4 and markedly elevated TSH results suggest primary hypothyroidism. Skeletal and
cardiac muscles are affected in hypothyroidism, causing the release of creatine kinase into the
circulation. This, combined with a decrease in the catabolic rate of creatine kinase, will be sufficient
to cause the creatine kinase to increase to the levels observed in this case. The aspartate
aminotransferase is mildly elevated and this will fall along with the creatine kinase and cholesterol
after a few weeks’ treatment with thyroxine. In view of the evidence of myocardial ischaemia it is
prudent to introduce thyroxine replacement cautiously (a low dose would be no more than 50 µg
daily). High initial doses can precipitate myocardial ischaemia, and where the hypothyroidism is
severe, as in this case, pericardial effusions and impaired ventricular function.
Case history 36
A 28-year-old woman with thyrotoxicosis has had two courses of carbimazole. Results from her recent
visit to the thyroid clinic now show:
TSH Free T4
mU/L pmol/L
<0.05 66
*It is likely that this patient has suffered a relapse of her thyrotoxicosis. The severity of the
derangement in her thyroid biochemistry (free T4 66 pmol/L) makes it likely that she will be clinically
thyrotoxic and symptomatic. Repeated failure of medical therapy may warrant consideration of
alternative treatment options, namely radioactive iodine and surgery. The former ablates the
production of thyroid hormones irreversibly, and the patient would need to take replacement
thyroxine therapy permanently thereafter.

Case history 37
A 40-year-old man was investigated for severe skeletal muscle pains. The following biochemical
results in a serum sample were unexpected:
Na+ K+ Cl– HCO3 – Urea Creatinine
mmol/L µmol/L
130 6.1 90 17 7.6 150
Suggesta likely diagnosis.
What other biochemistry tests might be helpful in the investigation of this patient?
* Whenever one encounters the combination of hyponatraemia with hyperkalaemia, adrenocortical
failure must be suspected. There is a modest increase in the serum creatinine with a normal serum
urea that is not typical of Addison’s disease. In adrenal failure the patient usually has pre-renal
uraemia, which causes the serum urea to rise more than the creatinine. The low serum bicarbonate is
a feature of adrenal insufficiency, and may reflect both the lack of mineralocorticoid activity and
lactic acidosis, the latter resulting from hypovolaemia and associated reduced tissue perfusion. It is
essential that, at the very least, a timed random cortisol is requested on this patient. Unless the result
is grossly elevated, thus excluding adrenal insufficiency, a Synacthen test is warranted. As the patient
has severe skeletal muscle pain the creatine kinase should be measured as the hyperkalaemia may be
due to potassium released from damaged muscle. If rhabdomyolysis were detected, it would be
important to monitor renal function and calcium status carefully.

Case history 38
A 31-year-old woman was admitted to a surgical ward with a 2-day history of abdominal pain and
vomiting. Her blood pressure was 110/65 mmHg and her pulse 88 beats per minute and regular. A
provisional diagnosis of intestional obstruction was made. On admission, tests showed:
Na+ K+ Cl– HCO3 – Urea Creatinine
mmol/L µmol/L
128 6.1 92 18 10.8 180
She was given 1.5 L of 0.9% saline intravenously, overnight, and the following morning her
symptoms had resolved. Her serum sodium had increased to 134 mmol/L and her serum potassium had
fallen to 4.8 mmol/L. On reviewing her history, it was found she had been unwell for a number of
months with weight loss and anorexia. She was noted to be pigmented. A short Synacthen test was
performed and the serum cortisol was less than 60 nmol/L both before and after an intravenous
injection of 0.25 mg of Synacthen.
Suggest the diagnosis How could the changes in her sodium and potassium be explained?
* This presentation is classical of acute adrenal failure with characteristic symptoms, physical
findings and electrolyte pattern. The diagnosis is confirmed by the Synacthen test. On presentation,
this woman was sodium depleted with pre-renal uraemia. As her ECF was expanded with 0.9%
sodium chloride, this improved her glomerular filtration rate, which is sufficient, even in the absence
of aldosterone, to correct the hyperkalaemia by increasing her urinary potassium excretion. The
reduction in this patient’s blood volume will stimulate vasopressin secretion, giving rise to the
hyponatraemia. The sodium chloride infusion by restoring her blood volume will inhibit AVP
secretion, enabling her to correct the hyponatraemia.

Case history 39
A 31-year-old woman presented with a 3-month history of weight gain, hirsutism, amenorrhoea and
hypertension. Her urine cortisol : creatinine ratio was increased, and serum cortisol diurnal rhythm
was absent. Treatment with 0.5 mg of dexamethasone q.i.d. did not suppress her cortisol, and insulin-
induced hypoglycaemia did not cause her serum cortisol to rise.
What investigations should now be carried out?
* Cushing’s syndrome is the most likely diagnosis in this case. One can be confident of the diagnosis
in view of the increased urinary cortisol : creatinine ratio, and the failure to suppress with low-dose
dexamethasone. Establishing a diagnosis of Cushing’s syndrome is insufficient as it is essential to
discover the underlying cause to enable the correct treatment to be given. This patient should have a
high-dose dexamethasone suppression test with measurement of serum cortisol and ACTH.
Suppression of the cortisol would point to the pituitary-dependent Cushing’s syndrome as would an
abnormally increased ACTH concentration. An adenoma should be actively sought in her pituitary
and adrenal glands by CT or MRI scanning. If her ACTH is abnormally increased she may undergo
selective venous catheterization to locate the source, which may be due to a carcinoid tumour of the
lung.

Case history 40
A 29-year-old woman complained of acne and irregular periods. On examination she was overweight
and moderately hirsute. Initial investigations showed a slightly elevated testosterone of 3.7 nmol/L.
LH was 15 U/L and FSH 5.6 U/L.
What other investigations should be undertaken to make a diagnosis in this patient?
* This clinical presentation combined with biochemical findings of increased testosterone, reduced
SHBG and increased LH/FSH ratio are characteristic of the polycystic ovarian syndrome. Ultrasound
examination of her ovaries would confirm the diagnosis. Patients with obesity and/or PCOS are
insulin resistant. This stimulates compensatory hyperinsulinaemia. In many insulinresistant women,
the ovaries remain relatively more insulin sensitive than other tissues, and the hyperinsulinaemia
stimulates ovarian androgen production.

Case history 61
A 30-year-old woman who had previously delivered one live child and had one miscarriage attended
for antenatal care. She was known to be rhesus negative. At 30 weeks’ gestation she was found to have
a high titre of anti-D antibodies.
What investigations should now be carried out?
*This woman should have an amniocentesis performed with bilirubin being measured in her amniotic
fluid. In Rhesus incompatibility the amniotic fluid bilirubin concentration will rise because of the
destruction of fetal red cells by maternal antibodies.
Case history 62
A 20-year-old woman in her first pregnancy was referred to hospital by her GP when she was 31
weeks pregnant. At 12 weeks pregnant she appeared well, had no oedema and her blood pressure was
110/70 mmHg. Now, she complained that she was unable to remove her wedding ring and that her
vision was blurred. On examination ankle oedema was also observed and her blood pressure was
found to be 180/110 mmHg.
What is the most likely diagnosis?
What sideroom test(s) should be performed?
What biochemical investigations should be performed immediately?
*Pre-eclampsia is the most likely diagnosis. The most appropriate side room test to perform would be
to test for albuminuria. Biochemical investigations that should be performed on this woman are:
Serum urate, as this is a sensitive indicator for pre-eclampsia. Serum urea and electrolytes should be
measured as she may be developing renal failure. Serum albumin and liver function tests should be
performed to detect liver disease.

Case history 63
The ‘blood spot’ analysis on a 6-day-old baby girl indicated a high TSH, 28 mU/L. A second blood
sample was quickly obtained for a repeat TSH estimation. The laboratory reported a TSH
concentration of 6 mU/L.
What investigations should now be carried out?
* No other investigations should be performed, but the parents should be reassured that their
daughter does not have congenital hypothyroidism. Over 99% of all 6-day-old children will have a
TSH of <10 mU/L while the majority of patients with congenital hypothyroidism will have a TSH
>100 mU/L. Babies with a blood TSH between 15 and 40 mU/L on their first test are considered to
have an equivocal result. If in a second sample a normal result is obtained, as is usually the case, no
further investigation need be made.

Case history 64
The baby of a diabetic mother weighed 1.64 kg (below 10th centile for weight) when born at
gestational age of 32 weeks. The baby was well at birth, but her condition deteriorated within hours
and she had respiratory problems
What biochemical determinations should be requested on this baby?
Why is it important to consider each request carefully?
*This baby’s blood gas status should be assessed as she is at risk of developing the respiratory
distress syndrome. In view of her maternal history, weight and gestational age, she may be
hypoglycaemic and her blood glucose should be measured. Hypocalcaemia is another possibility that
should be considered, so her serum calcium should be measured. The total blood volume in neonates
is small and could be less than 100 mL in this baby. It is, therefore, very important to collect the
minimum blood from neonates as they can become anaemic if a large number of investigations are
performed.