Should Free Thyroxine Go Back into the Routine Thyroid Profile?

BACKGROUND: Many clinical chemistry laboratories offer thyroid-stimulating hormone (TSH) alone as a first-line test of thyroid function, and only reflex a free thyroxine (fT4) test if the TSH result is abnormal (i. e., outside of the laboratory reference range). In secondary hypothyroidism, a low fT4 may be accompanied by a low or a normal TSH level. A testing strategy that measures baseline TSH only risks missing cases of secondary hypothyroidism in which the TSH level is normal. METHODS: The current authors examined 26,106 consecutive thyroid function test (TFT) results in our initial analysis. If the TFT results were compatible with hypopituitarism, with fT4 below the reference range (9-20 pmol/L) and a TSH result ≤5 mU/L (reference range: 0.5-5 mU/L), the laboratory performed further tests of pituitary function. The cost of identifying pituitary insufficiency by measuring both fT4 and TSH was estimated for our population (in 2004 and 2013) and compared with 2 other relevant studies. RESULTS: A total of 121 patients had a normal TSH with a low fT4. 8 new cases of secondary hypopituitarism were identified when fT4 was combined with TSH as the front-line TFT profile. Of these, 5 were found to have pituitary adenomas, 2 of which were macroprolactinomas. The reagent cost of identifying each case by inclusion of fT4 in the TFT profile decreased from £11,568 (€16,089) in 1998 to £1451 (€2018) in 2013. CONCLUSIONS: 8 cases of pituitary insufficiency would not have been identified with a strategy of TSH testing alone, which calls for the addition of fT4 to the routine TFT profile. The cost per case of identifying those with pituitary insufficiency by additional measurement of fT4 has become cheaper with time.

Most commercial insulin assays fail to detect recombinant insulin analogues.

Insulin assays are utilized in various clinical scenarios, including the assessment of insulin therapy compliance or of suspected insulin overdose. In an interpretative exercise carried out by UK National External Quality Assessment Service (NEQAS), serum sent to the participating laboratories was spiked with 30 pmol/L of the short-acting insulin analogue Human Actrapid. Only two out of 24 participant laboratories had sufficient assay cross-reactivity with Actrapid to interpret the results as suggestive of insulin administration. The development of specific insulin assays has led to deterioration in the ability to detect non-compliance or overdose with recombinant insulin treatment. Clinicians should be aware of this significant limitation, which could lead to misdiagnosis.

Acute non-immune haemolytic anaemia during infectious mononucleosis unmasking spherocytosis.

We report a case of acute haemolytic anaemia complicating infectious mononucleosis in a 19-year old male. There was no evidence for an immune haemolysis and red cell studies revealed a previously undiagnosed congenital spherocytosis. We discuss this rare presentation.

Meat consumption as a risk factor in enteritis necroticans.

The association between the consumption of animal protein and enteritis necroticans (EN) was investigated in a case-control study of 60 proven cases of acute surgical EN. A very high risk of EN was found in association with the recent ingestion of pork and other meats with the exception of tinned fish. The control group was characterized by the more frequent and regular ingestion of animal protein (predominantly in the form of tinned fish) suggesting a protective effect. No conclusions about the causality of the observed associations could be drawn but the implications for preventive intervention are discussed.

Effects of thymidine analogues on murine and human cells.

Three mouse tumour cell lines grew continuously in 3 micro M 5-bromodeoxyuridine (BUdR). One line (MC-2) produced a retrovirus and altered in morphology in the presence of BUdR or 5-iododeoxyuridine (IUdR). These effects, which could be reversed by growth in normal medium were similar to those reported for the B-16 mouse melanoma line. The B-16 line used in this study, however, as well as a variety of human cells (six melanoma lines and three fibroblast strains), were much more sensitive to BUdR, 0.03-0.1 micro M being the maximum tolerated levels for continuous growth. No virus production or changes in morphology were induced in these cells by BUdR, deoxyuridine (UdR), 5-fluorodeoxyuridine (FUdR) or thymidine (TdR). The results of cell labelling and growth studies showed a correlation of incorporation of BUdR into DNA with toxicity. Compared on a competitive basis with 1 micro M TdR, the order of incorporation of 1 micro M nucleosides by two human cell lines was TdR = BUdR = IUdR greater than UdR greater than FUdR. In contrast to previous reports that FUdR is incorporated into RNA but not into DNA, half of the FUdR label was found in alkalistable, DNase-sensitive material. Over 90% of the other compounds was incorporated into DNA. All of the UdR and 60% of the IUdR label was incorporated as thymidine; this conversion could be inhibited by labelling in the presence of FUdR.