ObjectiveTo comprehensively examine pathology test utilisation of 25-hydroxyvitamin D (25(OH)D) testing in each state of Australia to determine the cost impact and value and to add evidence to enable the development of vitamin D testing guidelines.DesignLongitudinal analysis of all 25(OH)D pathology tests in Australia.SettingPrimary and Tertiary Care.MeasurementsThe frequency of 25(OH)D testing between 1 April 2006 and 30 October 2010 coded for each individual by provider, state and month between 2006 and 2010. Rate of tests per 100 000 individuals and benefit for 25(OH)D, full blood count (FBC) and bone densitometry by state and quarter between 2000 and 2010.Results4.5 million tests were performed between 1 April 2006 and 30 October 2010. 42.9% of individuals had more than one test with some individuals having up to 79 tests in that period. Of these tests, 80% were ordered by general practitioners and 20% by specialists. The rate of 25(OH)D testing increased 94-fold from 2000 to 2010. Rate varied by state whereby the most southern state represented the highest increase and northern state the lowest increase. In contrast, the rate of a universal pathology test such as FBC remained relatively stable increasing 2.5-fold. Of concern, a 0.5-fold (50%) increase in bone densitometry was seen.ConclusionsThe marked variation in the frequency of testing for vitamin D deficiency indicates that large sums of potentially unnecessary funds are being expended. The rate of 25(OH)D testing increased exponentially at an unsustainable rate. Consequences of such findings are widespread in terms of cost and effectiveness. Further research is required to determine the drivers and cost benefit of such expenditure. Our data indicate that adoption of specific guidelines may improve efficiency and effectiveness of 25(OH)D testing.

Somatostatin (SRIF) and its analogs exert potent inhibitory effects on hormonal hypersecretion. In addition, they have been demonstrated to inhibit the proliferation of various cell lines as well as the growth of some endocrine tumors in vivo. To evaluate the action of SRIF and its analog octreotide on the proliferation and cell cycle kinetics of endocrine cells, we investigated their effect on GH3 rat pituitary tumor cells, a GH-producing cell line. Using flow cytometric DNA analysis with propidium iodide staining, we found that octreotide inhibits the proliferation of synchronized GH3 cells, achieving a maximal reduction, compared to controls, of 19.4 +/- 5.3% and 22.4 +/- 5.1% with 100 ng/ml and 1000 ng/ml octreotide, respectively (P < 0.05). This effect was demonstrated to be due to a block in progression from the G0/G1 phase to the S phase of the cell cycle. This was most evident after 24 h of exposure to 100 ng/ml octreotide, at which time there was a 7.1 +/- 1.4% increase in cells in G0/G1 (P < 0.01) and a 6.6 +/- 1.3% decrease in cells in S phase (P < 0.01). However, unless octreotide was replenished, this effect was transient and overcome by 36-48 h. No apoptosis was seen, and trypan blue studies confirmed that cell death by necrosis did not occur. A single exposure to native SRIF-14 had little effect, but a G0/G1 cell cycle block and inhibition of proliferation were seen if SRIF was regularly replenished. We conclude that SRIF and octreotide exert a cytostatic effect on GH3 cells by causing a partial G0/G1 cell cycle block. These findings suggest that the actions of SRIF and octreotide occur through signal transduction pathways that act predominantly on downstream regulators.

Octreotide failed to significantly reduce 24-hour urinary free cortisol, serum cortisol and ACTH in the two patients reported. We conclude that it should probably not be regarded as primary treatment for control of hypercotisolism in patients with ACTH-producing carcinoids, but reserved as adjunctive therapy.

Goiter is a frequent clinical finding in patients with acromegaly, an effect mediated by chronically elevated insulin-like growth factor I (IGF-I) levels. It is unclear, however, whether the presence of TSH is a prerequisite for the growth-promoting actions of IGF-I on the human thyroid. We, therefore, studied a group of subjects with hypopituitarism, who were deficient in both TSH and GH, examining the effects of GH replacement therapy on thyroid size and function. GH replacement was initiated in 14 subjects with hypopituitarism. After 6 months of recombinant human GH therapy at 0.25 IU/ kg week, IGF-I levels increased from 11.5 +/- 6.0 to 32.4 +/- 15.4 nmol/L (P = 0.002). Thyroid volume, as determined by ultrasound, did not change significantly over this period. Similarly, there was no change in thyroglobulin levels after treatment with GH, but there was a decrease in the free T4/free T3 ratio (P = 0.043). Pretreatment thyroid size in subjects with hypopituitarism was also compared to that in a group of age- and sex-matched controls. The size of thyroid glands in the hypopituitarism group was smaller than that in controls (P = 0.015). We found that GH therapy did not increase thyroid size in patients with hypopituitarism. From these data we conclude that in vivo, IGF-I does not independently stimulate thyroid growth, but promotes thyroid cell proliferation by potentiating the mitogenic action of TSH.