G.H. Beastall

Alteration of the circadian rhythm of intact parathyroid hormone following a 96‐hour fast

OBJECTIVE PTH(1‐84) secretion in normal male subjects follows a circadian rhythm. The control of this rhythm is multifactorial with both neuroendocrine and chemical influences. The aim of this study was to assess the effect of a 96‐hour fast on the circadian rhythm of PTH(1 ‐84), serum calcium, phosphate and nephrogenous cAMP (NcAMP), an index of PTH(1‐84) bioactivity.

Direct and indirect assessment of the parathyroid hormone response to pamidronate therapy in Paget's disease of bone and hypercalcaemia of malignancy

In patients with either Pagets disease or hypercalcaemia associated with malignancy (HCM) we have assessed the parathyroid response to pamidronate therapy, both by immunoassay of serum intact parathyroid hormone PTH (1-84) and by measurement of indirect parameters of PTH bioactivity, tubular maximum reabsorption of phosphate (TmPO4/GFR) and nephrogenous cyclic AMP (NcAMP). In 12 patients with Pagets disease, therapy with pamidronate produced a small but significant decrease in adjusted serum calcium within the reference interval which was accompanied by a progressive increase in PTH (1-84) secretion and a corresponding fall in TmPO4/GFR and increase in NcAMP. In 12 patients with HCM pretreatment, PTH (1-84) concentrations were suppressed, whilst mean TmPO4/GFR was reduced and NcAMP was increased, compatible in most patients, with parathyroid hormone-related peptide (PTHrP) driven hypercalcaemia. Therapy with pamidronate produced the expected fall in serum calcium but caused an increase in PTH (1-84) secretion in the presence of absolute hypercalcaemia. The initial subnormal TmPO4/GFR decreased further to a nadir on day 5, and there was a corresponding further increase in NcAMP. By day 7, however, when PTH (1-84) concentrations were maximal, there was a significant paradoxical rise in TmPO4/GFR and a corresponding decrease in NcAMP. These data are consistent with a variable trigger point for PTH (1-84) secretion, one consequence of which is a reduction in the risk of hypocalcaemia following pamidronate. The results have major clinical implications for the interpretation of PTH (1-84) measurements in patients who are being treated or about to be treated for bone disease or for hypercalcaemia of malignancy (HCM).(ABSTRACT TRUNCATED AT 250 WORDS)

THE LOSS OF CIRCADIAN RHYTHM FOR INTACT PARATHYROID HORMONE AND NEPHROGENOUS CYCLIC AMP IN PATIENTS WITH PRIMARY HYPERPARATHYROIDISM

The measurement of serum intact parathyroid hormone (PTH) (1‐84) over a 24‐h period has shown the existence of a circadian rhythm in normal males which is absent in patients with primary hyperparathyroidism. The physiological significance of this observation is reflected in the presence of parallel changes in nephrogenous cyclic adenosine monophosphate (N‐cAMP) in normals which are also absent in primary hyperparathyroidism. Serum calcium, adjusted for variations in albumin concentrations, showed a transient fall in normal subjects prior to the nocturnal rise in PTH (1‐84). A similar transient fall in serum adjusted calcium was observed in the hyperparathyroid patients. Serum phosphate showed a circadian rhythm in normal subjects, and an attenuated rhythm persisted in primary hyperparathyroidism. These data suggest that both ionic factors and higher centres play important roles in the fine control of PTH (1‐84) secretion.

EFFECTS OF TREATMENT WITH OESTRADIOL/LEVONORGESTREL ON BONE, LIPOPROTEINS AND HORMONE STATUS IN POSTMENOPAUSAL WOMEN

The aim of the study was to investigate the effects of an oestradiol/ levonorgestrel regimen, administered parenterally, on bone metabolism, bone density, lipoprotein metabolism and hormone status. Twenty‐five women who had undergone a surgical menopause had an oestradiol/levonorgestrel‐containing vaginal ring pessary in situ for 6 months. Within the first month there were sustained changes in the biochemical indices of bone metabolism in keeping with a marked reduction in bone turnover and decrease in bone resorption. Bone mineral content in the distal forearm was measured in 14 patients and a small increase was noted in every patient. Levonorgestrel was well absorbed and the serum levels remained almost constant throughout treatment. There was a gradual increase in serum total oestradiol which became significant at 6 months. Dialysable oestradiol levels rose from 26% of total oestradiol at 0 time to 3.3% at 1 month with no further change thereafter. SHBG levels were 23% of pretreatment levels at 6 months. There were sustained decreases in triglyceride, VLDL and HDL cholesterol levels and a transient fall in LDL cholesterol. Total HDL, HDL2 and HDL3 cholesterol levels were reduced by 25, 40 and 21% respectively. The results suggest that levonorgestrel exerts a protective influence on bone either directly or by its effect on the proportion of oestradiol circulating in the free, physiologically active form. The effects on lipoproteins were predominately those of the progestogen component, the lipoprotein risk factors for coronary heart disease being adversely affected.

Sex steroid replacement in post-menopausal women: effects on thyroid hormone status

We have measured serum thyroxine (T4), triidothyronine (T3), thyroid-stimulating hormone (TSH) free thyroxine (FT4) and thyroxine-binding globulin (TBG) levels in a total of 5 post-menopausal women who were receiving oestrogen alone (Premarin, n = 19), progestogen alone (Primolut-N, n = 12), a combination of oestrogen and progestogen (Prempak C, n = 14) or no treatment (control group, n = 12). No differences were observed between the Premarin and Prempak C groups; both exhibited elevated T4 and TBG levels, although free thyroxin (FT4) and T4/TBG concentrations were normal relative to those in the control group. The Primolut-N subjects showed subnormal T3 and FT4 levels relative to the controls. It was concluded that it is not possible to make general statements regarding the effects of sex steroids on FT4 levels.

Organon OD 14 (Tibolone) and menopausal dynamic hormone profiles

Hormonal profiles were studied in 15 post-menopausal women, 7 of whom had been treated with Organon OD 14 (Tibolone) and 8 with placebo tablets for 3 yr. In the Tibolone-treated group, the sex hormone binding globulin (SHBG) levels were significantly lower, while the estimated free testosterone levels, the testosterone/SHBG ratio and the thyroid-stimulating hormone (TSH) response to thyrotrophin-releasing hormone (TRH) were significantly higher than in the placebo group. Prolactin and triiodothyronine (T3) concentrations were lower in the actively treated group, although the differences were not statistically significant. No significant differences were observed with respect to thyroxine (T4), TSH, basal cortisol or cortisol response to synacthen.

Effects of treatment with oestradiol/levonorgestrel on bone, lipoproteins and hormone status in post-menopausal women

The aim of the study was to investigate the effects of an oestradiol/levonorgestrel regimen, administered parenterally, on bone metabolism, bone density, lipoprotein metabolism and hormone status. Twenty-five women who had undergone a surgical menopause had an oestradiol/levonorgestrel-containing vaginal ring pessary in situ for 6 months. Within the first month there were sustained changes in the biochemical indices of bone metabolism in keeping with a marked reduction in bone turnover and decrease in bone resorption. Bone mineral content in the distal forearm was measured in 14 patients and a small increase was noted in every patient. Levonorgestrel was well absorbed and the serum levels remained almost constant throughout treatment. There was a gradual increase in serum total oestradiol which became significant at 6 months. Dialysable oestradiol levels rose from 2.6% of total oestradiol at 0 time to 3.3% at 1 month with no further change thereafter. SHBG levels were 23% of pretreatment levels at 6 months. There were sustained decreases in triglyceride, VLDL and HDL cholesterol levels and a transient fall in LDL cholesterol. Total HDL, HDL2 and HDL3 cholesterol levels were reduced by 25, 40 and 21% respectively. The results suggest that levonorgestrel exerts a protective influence on bone either directly or by its effect on the proportion of oestradiol circulating in the free, physiologically active form. The effects on lipoproteins were predominately those of the progestogen component, the lipoprotein risk factors for coronary heart disease being adversely affected.