SUMMARY.Blood was taken from normal subjects at monthly intervals over a period of one year for subsequent determination of serum thyroid hormone concentrations. Thyroid-stimulating hormone (TSH) responses to TSH-releasing hormone were performed at 3-monthly intervals. This study provided data on within-individual variation and on seasonally-related changes of these thyroid function tests.The results showed that, within an individual, thyroid hormone concentrations are maintained within narrow limits. For both thyroxine and triiodothyronine the component contribution of within-individual variation to the population-based variation (the latter also termed the 'reference interval', or colloquially the 'normal range') was small. This high degree of individuality implies that rigorous comparison of thyroid hormone results against a population-based 'normal range' can be potentially misleading.Despite the limited within-individual variation, seasonally-related changes in thryoid hormone concentrations were apparent, with higher thyroxine and triiodothyronine values seen in winter months. A tendency to a greater TSH response to TSH-releasing hormone was also noted at this time. Conceivably these changes could reflect a centrally-mediated response of the hypothalamic-pituitarythyroid axis to environmental temperature.Laboratory 'normal ranges' are usually based on results from a group of healthy subjects and, for data showing a Gaussian distribution, conventionally embrace values extending to two standard deviations from the mean value. It is well recognised, however, that withinindividual variation of many biochemical tests is considerably less than the population-based reference interval (usually referred to as the 'normal range').l-4 We have studied withinindividual variation of serum thyroid hormone concentrations over a 13-month period; in addition, this investigation has allowed us to determine the extent of any seasonal influence on thyroid hormone values. Thyroid-stimulating-hormone-releasing hormone (TRH) tests were performed at intervals during the study. MethodsSix normal subjects (three male, three female) took part. Blood was taken without venous stasis" from each subject, who was seated quietly at the time of venepuncture. The samples were taken during the first 10 days of each calendar month for 13 months (OctoberOctober), and from each subject at the same time of day. Sera were stored at -20°C until the end of the study and those from each subject were assayed in a single batch to eliminate between-assay variation. Studies in this laboratory have confirmed other reports": 7 that serum thyroid hormones are stable under these conditions for at least one year. TRH tests were conducted using a 200 J.lg bolus intravenous injection (TRH, Roche Products Ltd) and blood was taken before and at 10, 20, 30, 45 and 60 min after TRH; these tests were performed every three months at 0, 3, 6 and 12 months of the study. An exceptionally cold period occurred between 2 and 3 months after the conclusion of the study and t...

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We compared the utility of a sensitive immunoradiometric assay for serum thyrotropin as a "first-line" thyroid-function test with a strategy based on first measuring total thyroxin in serum. The immunoradiometric assay appears to distinguish primary hypothyroidism and hyperthyroidism from euthyroidism in "new" patients. The role of this test in monitoring antithyroid treatment or thyroxin-replacement therapy is not yet established, there being particular difficulty in interpreting low thyrotropin concentrations in such patients. Nevertheless, because a normal thyrotropin concentration in most, if not all, situations signifies the euthyroid state, thyrotropin determination by immunoradiometric assay merits consideration as an initial test by laboratories performing thyroid-function tests.

SUMMARY Over a period of one year, 24 500 patients underwent a biochemical profile investigation. Seven hundred and thirty-eight (3 %) patients had a plasma calcium concentration of greater than 2-60 mmol/l, and hypercalcaemia was confirmed in 49-8 % of those subjects from whom a second fasting sample was received. Primary hyperparathyroidism and malignant disease were the two commonest causes of hypercalcaemia, occurring with equal frequency. The overall incidence of primary hyperparathyroidism in our population was 1:680. Over 75 % of the patients with primary hyperparathyroidism appeared to have asymptomatic disease. The merits of including a plasma calcium determination in a biochemical profile would seem to depend particularly on the natural history of asymptomatic primary hyperparathyroidism.In 1976 a multichannel analyser was commissioned in our Department and a plasma calcium determination has been included as one of the 14 tests performed on each blood sample submitted for a biochemical profile. In view of several reports describing increased recognition of hypercalcaemia following the introduction ofbiochemical screeningl-4 we conducted over a period of one year a study of patients whose biochemical profile indicated hypercalcaemia. We have looked in particular at the causes of hypercalcaemia and the occurrence of primary hyperparathyroidism. Patients and methodsThe study year extended from 1 October 1978 to 30 September 1979. Samples from patients over the age of 15 y on whom, at the clinician's request, a proffie analysis was performed for the first time during this period were included. Plasma calcium was measured by the method of Gitelman5 modified for use on the Vickers M300 analyser. Our upper limit of normal for plasma calcium is 2 60 mmol/1; this value, representing 2 SD above the mean, was confirmed in samples taken without venous stasis from 50 healthy, ambulant control subjects at the Accepted for publication 27 July 1981 start of the study. When this level was exceeded the referring clinician was invited to submit a fasting sample taken from the patient without venous stasis for a second profile.Plasma PTH was measured by immunoradiometric assay,6 using a predominantly C-terminal antiserum (BW211/41) and a reference preparation of human PTH (75/549) as standard. The sensitivity of the assay was 0-15 ,ug/l and the between-batch coefficients of variation at 0 2 ,ug/l and 1-0 ,ug/l were 13 % and 8 % respectively. The upper limit for PTH in normocalcaemic subjects is 1 ,ug/l. The tubular maximum reabsorptive capacity for phosphate relative to glomerular filtration rate (TmP/GFR) was estimated by the method and nomogram of Walton and Bijvoet.7 The reference range for TmP/GFR was defined in 30 normal subjects as 0 75 to 1-30 mmol/l. The progress of patients with fasting hypercalcaemia was assessed, mostly by inspection of the clinical notes, at least six months after the date of their inclusion in the study. ResultsBiochemical profiles were performed on samples from 24 500 patients. Of these 75% ...

Parathyroid hormone related protein (PTHRP) has been implicated in humoral hypercalcaemia of malignancy (HHM). We describe a patient with a renal carcinoma and hypercalcaemia, and for the first time have demonstrated a 4-fold PTHRP concentration gradient across a renal tumour bed. This provides further strong evidence that the primary tumour was the source of the PTHRP. The PTHRP 1-86 content of the tumour tissue was 4.8 ng/g, similar to that previously found in tumours associated with HHM. In PTHRP-secreting tumours, PTHRP may be a useful oncological marker after surgical resection.