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Purpose To investigate changes in bone mineral density (BMD) following denosumab after previous bisphosphonate therapy and the impact of chronic kidney disease (CKD) on response. Methods A retrospective study of 134 patients (11 M, 123 F) aged [mean (SD)] 72 [11] years on denosumab was undertaken. Ninety-five patients had previously been on oral and 28 on iv bisphosphonate. Lumbar spine (LS), total hip (TH) and femoral neck (FN) BMD were measured before treatment and at 2.7 [1.2] years. GFR was Results BMD improved following denosumab [mean (SEM) % change LS: 6.0 (0.62) p p p = 0.045]. Changes at the TH and FN were lower in patients with GFR 35 ml/min (Group A) [% change TH; Group A: 2.9 (0.72), Group B: − 0.84 (1.28), p = 0.015, FN; Group A: 2.76 (0.86), Group B: − 1.47 (1.53), p = 0.025]. % change in BMD at the FN and PTH were negatively associated (r = − 0.25, p = 0.013). BMD changes were not different at 12–18 months between patients on denosumab compared to zoledronate [% change at LS: denosumab: 3.97% (0.85), zoledronate: 2.6% (0.5), p = 0.19 TH: denosumab: 0.97% (0.58), zoledronate: 0.92% (0.6), p = 0.95). Conclusion Denosumab increases BMD following previous bisphosphonate treatment and is comparable to zoledronate. Lower response seen at the hip in CKD is related to PTH concentrations.

We have examined the utilisation of glucose and ketone bodies in normal adipose tissue in response to insulin and some drugs used in diabetic therapy. Under basal conditions 14C from acetoacetate was incorporated into long chain fatty acids, while 14C from glucose was found principally in the glyceride glycerol fraction of tissue lipids. Fatty acid synthesis from acetoacetate was stimulated ten-fold by glucose addition up to 20m.M and conversely, acetoacetate enhanced the incorporation of glucose 14C into lipids. The stimulatory effect of glucose was independent of its transport, since it is not reproduced by 2-deoxy-glucose. Insulin further stimulated fatty acid synthesis from acetoacetate, an effect abolished in the absence of glucose. Phenethyl-biguanide (Phenformin) increased tissue glucose uptake, although it decreased glucose 14C and acetoacetate 14C incorporation into triglyceride. Free fatty acids (FFA) and very low density lipoproteins (VLDL) addition at concentrations observed in diabetic ketosis resulted in inhibition of acetoacetate utilisation. We conclude that ketone bodies do not block glucose utilisation in normal human adipose tissue in vitro. The apparent reduction in ketone body metabolism during diabetic ketosis may be related to the high FFA and VLDL levels observed.

A combined test consisting of the simultaneous administration of insulin, thyrotrophin-releasing hormone (TRH), and luteinizing hormone and follicle stimulating hormone-releasing hormone (LH/FSH-RH) was performed in 24 people. Eleven of these also had the three individual tests performed separately, and the remaining 13 had a separate test of either LH/FSH-RH and TRH together or singly at a later date. In both normal people and patients, whether the tests were performed alone or in combination, no difference was found between the hormone responses (growth hormone, cortisol, LH, FSH, thyroid-stimulating hormone) seen to these stimuli. It is proposed that combined administration of insulin and the hypothalamic releasing hormones may be used as a single test for the assessment of anterior pituitary function. The test is convenient and time saving, and with care can be performed in outpatients.

Seven patients with anorexia nervosa were studied, three during the acute stages of the illness, and four in whom weight gain had been achieved, but who suffered from persistent amenorrhoea of 18 to 79 months' duration.In the acute stage all patients had low serum luteinizing hormone (LH) levels which were unresponsive to clomiphene citrate. In those who had regained weight the mean basal LH levels were normal, and they responded to clomiphene with an initial doubling of serum LH during administration of the drug, followed by a second peak of serum LH four to seven days after the drug was stopped. Menstruation occurred in these patients 13 to 19 days after the clomiphene was discontinued, and in two patients regular spontaneous menstruation was initiated.The low LH levels unresponsive to clomiphene in the acute stage provide evidence for a hypothalamic abnormality in anorexia nervosa. After regain of body weight the drug seems to be effective in treating the amenorrhoea which may be persistent.

Ninety-four growth hormone deficient New Zealand children were treated with thrice weekly intramuscular injections of human pituitary growth hormone (GH) from 1979 to 1985 and the results from 43 children were analysed in detail. Their height velocity was mean (SD) 4.0 (1.9) cm/yr immediately prior to treatment and 8.5 (3.1) cm/yr in the first year of treatment. In each of the first three years of treatment the height velocity was significantly increased (p less than 0.001), but there was a significant decline in height velocity between the first and second, and second and third years. Nevertheless each year of treatment gave a highly significant gain in relative height. Bone age did not advance more rapidly than chronological age during the first two years of treatment, but did so subsequently. The response to GH, as assessed by the increase in relative height, was negatively correlated with the relative height at the start of treatment and with the maximum pretreatment plasma GH response to insulin hypoglycaemia. There was no correlation with pretreatment relative height velocity or aetiology of GH deficiency. Height velocity improved in five of 14 children treated with thyroxine after starting GH. Discontinuation of GH for one year in 34 children resulted in a highly significant reduction in growth rate from 7.5 (2.4) cm/yr to 2.5 (2.0) cm/yr, however four prepubertal children continued to grow at a rate exceeding 4 cm/yr.

Hyperprolactinaemia was found in all 17 women and in one out of six men who presented with hypogonadism and a radiologically enlarged sella turcica but no other clinical endocrine dysfunction. Some of the women also had galactorrhoea. The greater the level of hyperprolactinaemia in these 18 patients the larger their sellae turcica except in two patients with unusual features. The sella turcica was usually asymmetrically enlarged and there was rearly an upward extension of tumour, though the sella floor often showed some erosion on tomography. An oral dose of bromocriptine suppressed the hyperprolactinaemia in mose patients at the same rate as in normal post-partum women. Nine of the 18 patients with hyperprolactinaemia had low basal luteinizing hormone (LH) levels. The LH responsiveness to 100 mug of LH-releasing hormone (LHRH) was tested in 12, and eight showed subnormal values. Of eight biopsy specimens obtained four showed acidophil granules on light microscopy, and in five granules of various sizes were seen on electron microscopy.

The effects of administration of methyldopa on serum prolactin and growth hormone (GH) concentrations in hypertensive patients were studied. Single doses of methyldopa (750 or 1000 mg) significantly increased serum prolactin levels, peak concentrations occurring four to six hours after drug administrations. Long-term methyldopa treatment was associated with threefold to fourfold increases in basal prolactin levels compared with those in normal subjects. In patients treated with methyldopa for two to three weeks the GH response to insulin hypoglycaemia was significantly greater than in normal subjects and untreated hypertensive patients. In contrast, patients treated for prolonged periods (mean 13-4 months) had a GH reponse indistinguishable from normal.

Insulin has been reported as extractable from the pancreas of human foetus from 10--12 weeks gestationM age [3, 6], or about the period when islet cells can be clearly seen in sections [3, 5, 4]. But insulin synthesis has been reported to procede B granulation in the pancreas from human foetuses [3], as well as in those of rat, rabbit, mouse and hamster [2]. Also one report mentioned tha t insulin was demonstrable in the heart blood of a 12 week old human foetus [6]. As endogenous insulin secretion may play an important role in foetal growth, i t seemed important to assess the pancreatic content of insulin a t different gestational periods. But the available reports have dealt only with a few observations and have not assessed the pancreatic insulin content in relation to age. The present paper reports the immunoreactive insulin (IRI) content of 203 pancreases from human foetuses aged 11--27 weeks.

Preliminary treatment with carbimazole in a series of 181 patients with thyrotoxicosis selected for treatment with radioactive iodine did not make any significant difference to the subsequent response to (131)I therapy.