Serum insulin-like growth factor I in a random population sample of men and women: relation to age, sex, smoking habits, coffee consumption and physical activity, blood pressure and concentrations of plasma lipids, fibrinogen, parathyroid hormone and osteocalcin

OBJECTIVE There Is a cllnlcal need for population based reference values for serum Insulin-like growth factor I (IGF-I). We have therefore determined serum IGF-i concentrations In a random population sample from Sweden and have related the levels to age, sex, llfe style factors, blood pressure, body composition, blood llplds, plasma fibrlnogen, Parathyroid hormone (PTH) and osteocalcin. PATIENTS Wlthln the framework of the WHO MONICA Project In the city of Göteborg, Sweden, 197 men and 195 women aged 25–64 years were studied. RESULTS Women aged 25–34 years had higher IGF-I concentration than men (mean 278 vs 227 μg/l) but In the interval 55–64 years values were lower In women than In men (158 vs 171 μg/l). IGF-I correlated positively with height and inversely with age, body mass Index, systolic blood pressure and total cholesterol in both sexes. Negative relations between IGF-I and hlgh density llpoprotelncholesterol, as well as with amount of tobacco smoked, were found in men, and between IGF-I and diastolic blood pressure, triglycerldes and PTH in women. When age was allowed for in multivariate analyses, most of these relations disappeared. However, among men IGF-l was positively assoclated with flbrlnogen and negatively with age and smoking. IGF-I was negatively assoclated with age and coffee consumptlon in women. CONCLUSION The present data can be used as reference values for IGF-I (at least in Caucasians) for the diagnosis of growth hormone dlsturbances and as guidelines for growth hormone substitution.     

Brain biopterin metabolism in chronic experimental hepatic encephalopathy

Chronic hepatic encephalopathy (HE) is a neuropsychiatric syndrome associated with a substantial increase in the brain L-tryptophan (L-TRP) level. Moreover, a supranormal L-TRP hydroxylating activity in the brain suggests an induced enzymatic process in chronic HE. GTP-cyclohydrolase I (GTPCHI) and tetrahydrobiopterin (BH4) are two major factors besides L-TRP that are involved in regulating the brain L-TRP hydroxylating activity. We therefore determined the GTPCHI activity, the total biopterin and the BH4 concentrations in the neocortex and mesencephalon-pons of portacaval shunted (PCS) rats. The encephalopathic component in PCS rats was accounted for by studying open field behaviour. The acute effects of a single parenteral L-TRP challenge were also evaluated. The basal GTPCHI activities in PCS rats were decreased bu 50% (p<0.05) compared to controls in both investigated brain regions. No significant alterations in brain total biopterin or BH4 levels were present. The PCS rats exhibited a clearly reduced spontaneous locomotor activity. After the exogenous L-TRP load only a lower GTPCHI activity in the neocortex of PCS rats was recorded. We conclude that a perturbation in the brain biopterin metabolism is concomitantly present with behavioural abnormalities in the chronic PCS condition and that the acute effects of a superimposed L-TRP load do not aggravate these disturbances.     

Aspects of hormone replacement therapy in the post-menopause

A review of the literature indicates that hormone replacement therapy (HRT) in post-menopausal women not only reduces the frequency of hot flushes and sweating episodes but also has a protective effect as regards the post-menopausal osteoporotic process. However, it has not yet proved possible to arrive at any conclusions concerning the overall effect of HRT on either ischaemic heart disease and other cardiovascular problems or the risk of developing malignant neoplastic disease. Nevertheless, there is evidence that oestrogen replacement in combination with a progestogen will reduce the risk of endometrial and breast cancer. There is a clear need for additional knowledge and it would therefore seem ethically appropriate to carry out an intervention study in order to determine whether women in general or specific groups in particular would benefit from long-term HRT. Such a study would seem especially urgent, since fractures of the neck of the femur and other osteoporotic manifestations are likely to be a major problem among women in the future.     

Diagnosis of early glaucoma with flicker comparisons of serial disc photographs

We evaluated flicker comparison, a technique for detecting differences in serial fundus photographs. Serial optic disc photographs and computerized threshold visual fields were obtained every 3 months for an average of 40 months in 131 eyes of 81 patients with elevated intraocular pressure and normal visual fields. Two serial monophotographs were projected, optically aligned, and superimposed; analysis was done by alternately viewing first one and then the other image. We found flicker analysis of serial disc photographs to provide results which were closely correlated with those of computerized threshold perimetry. Thus, of those 12 eyes which developed field defects, eight showed definite change and two showed highly suspected change in optic disc configuration. Only two eyes showed a definite alteration in optic disc anatomy without the development of field loss, and field defects appeared in only one of 109 eyes in which there was no change or suspected change on flicker comparison. The flicker method was more sensitive than conventional nonflickered comparisons, but changes could usually be seen also with conventional inspection once they had been detected by the flicker method. Our findings suggest that flicker analysis may offer a considerable improvement over current standard methods of analyzing serial photography and may be a useful complement to routine perimetry. However, this method requires special equipment; requires that the photographs be similarly centered; and is time-consuming. Alignment of photographs by means of computerized image analysis techniques could make the method clinically practicable.     

Nuclear DNA-content of parathyroid cells in adenomas, hyperplastic and normal glands.

Nuclear DNA-content in parathyroid cell imprints from adenomas, hyperplastic and normal glands was determined. Two principally different staining procedures were applied: paratoseaniline-Feulgen and ethidium-bromide staining. All nuclei, particularly with the ethidium-bromide method were registered as containing even multiples of the normal human diploid DNA-content. Normal and hyperplastic glands showed greater than or equal to 98 per cent diploid nuclei, the remaining fraction was tetraploid. In adenomas the frequency of diploid nuclei varied from 50-98 per cent; the remaining were predominantly tetraploid, but octaploid and higher even ploidity also occurred. A good correlation was found between nuclear DNA-content and nuclear diameter. The findings indicate that determination of nuclear DNA-content of parathyroid cells may be a valuable contribution in the differentiation between hyperplasia and adenoma.     

The prevalence of glaucoma.

The occurrence of glaucoma was studied in a population comprising 1963 persons born during 1907 to 1921 and living in a small Swedish suburban and rural district. The records of 24 patients treated for glaucoma were examined. An estimate of the prevalence of glaucoma in untreated persons was based on an examination of 1511 subjects by standardised methods (including automatic perimetry) and strict diagnostic criteria. About 20% of all cases of glaucoma with visual field defects in the whole population were already known. Only 7 out of 15 cases of previously unknown but manifest glaucoma had intraocular pressures above 20-5 mmHg. The reduction in visual capacity caused by glaucoma in the present population was limited.     

Acromegaly and Cushing's syndrome due to ectopic production of GHRH and ACTH by a thymic carcinoid tumour: in vitro responses to GHRH and GHRP-6

A 50-year-old male presented with diabetes mellitus and Cushing's syndrome associated with a large mediastinal mass. The levels of serum cortisol were high (1500–1800 nmol/l) without diurnal variation. Plasma ACTH levels (200–250 ng/l) and urinary excretion of cortisol were also increased. The levels of these hormones did not change in response to stimulation with corticotrophin releasing hormone (CRH) or suppression with high doses of dexamethasone. The patient had an elevated baseline GH level (7.3 mU/l), and the levels of immunoreactive GH-releasing hormone (GHRH) in eight plasma samples were markedly increased (600–1500 ng/l). Circulating levels of IGF-1, chromogranin A and neuropeptide Y (NPY) were also increased. Computer-assisted tomography and octreotide scintigraphy revealed a large mediastinal tumour and metastases in the left supraclavicular fossa. During treatment with octreotide, the baseline GH level was decreased (to 4.4 mU/l), while the GH pulse height was unchanged. Surgical removal of most of the tumour tissue resulted in a further decrease in the baseline serum GH level to a value (1.6 mU/l) about 20% of that before treatment, while the pulse height and mean GH were affected to a lesser extent. Postoperatively, circulating levels of cortisol and IGF-1 decreased, and the patient exhibited clinical improvement. Histological examination showed a neuroendocrine tumour with characteristics consistent with a foregut carcinoid of thymic origin. Immunoreactive GHRH, ACTH and NPY, but not immunoreactive GH, were detected in 80–90% of the tumour cells and the three peptides appeared to be co-localized. In primary culture, cells from this tumour displayed calcium influx in response to GHRH or GH releasing peptide-6 (GHRP-6), while there were not such responses by cells from another carcinoid not producing GHRH, ACTH or NPY. These results demonstrate a rare case of ectopic production of GHRH, ACTH and NPY, and indicate that the tumour cells were responsive to GHRH and GHRP-6 as well as octreotide.     

Idiopathic eosinophilic myositis associated with vasculitis and symmetrical polyneuropathy

We present a 79-yr-old white woman admitted to the hospital with diffuse myalgias and muscle weakness associated with eosinophilia. Examination of a muscle biopsy section revealed eosinophilic myositis with vasculitis. This association is infrequent and we describe the first case report with symmetrical polyneuropathy. The treatment with prednisone (60 mg/day) led to a complete clinical-pathological recovery of the disease. We review the differential diagnosis and the aetiopathogenic mechanism.