bluuebunny/crossref_metadata_2025 huggingface dataset:
THE HORMONE RESPONSE TO A SYNTHETIC ANDROGEN (MESTEROLONE) IN OLIGOSPERMIA
Authors: JACKAMAN F. R. , ANSELL I. D. , GHANADIAN R. , McLOUGHLIN P. V. A. , LEWIS J. G. , CHISHOLM G. D.
Published: March 2008

Forty subfertile men with oligospermia were treated with a synthetic androgen (Mesterolone). The effect of the drug was evaluated by measuring serum testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH) and analysing the semen before and after treatment. The results demonstrated that in twenty‐three patients treated for 6‐9 months there was a significant decrease in serum testosterone (P<0.01); the means ± SEM before and after treatment were 17.05 ± 0.95 and 14.7 ± 0.95 (nmol/1 serum) respectively. There was a pronounced increase in serum LH (P<0.01), the values being 2.73 ± 0.26 and 3.61 ± 0.3 (u/l) respectively. However, no significant difference was found in serum FSH before and after treatment. The sperm concentration showed a variable response to treatment. In twenty‐one patients there was either no change or worsening in the sperm concentration, whereas in nineteen patients an improvement was observed. The analysis of variance of sperm concentration and motility for the periods before and after treatment, for all the patients, showed no significant difference in the sperm concentration F1.145=2.82 (P= 0.1).

Various drugs have been used to improve the seminal quality in oligospermic males in whom no obvious cause can be found. These drugs have included human gonadotrophins, clomiphene, corticosteroids and androgens (testosterone, methyl‐testosterone, fluoxymesterone and Mesterolone). Mesterolone (Proviron) is a synthetic steroid (17β‐hydroxy‐1α‐methyl‐5α‐androstan‐3‐one) which is thought to contribute to the androgen pool but not to be recognized by the hypothalamus/pituitary system and not to suppress endogenous androgen production through reducing pituitary gonadotrophins (Petry et al., 1968; Gerhards et al., 1968).

Improvement in the quality of semen by Mesterolone has already been reported (Schellen & Beek, 1972; Somerville & Hendry, 1972; Barwin et al., 1973) but there has been no detailed study of serum gonadotrophin and testosterone levels during a clinical trial with this drug. This study was designed to investigate the effect of Mesterolone on (1) the semen analysis and (2) the serum hormone values (FSH, LH and testosterone) during treatment.
HYPOTHALAMIC‐PITUITARY‐OVARIAN FUNCTION IN PERIMENOPAUSAL WOMEN
Authors: VAN LOOK PAUL F. A. , LOTHIAN HELEN , HUNTER WILLIAM M. , MICHIE EILEEN A. , BAIRD DAVID T.
Published: March 2008

In a group of nine perimenopausal women, aged 37–52 years, with dynsfunctional uterine bleeding (DUB), serial measurements were made of urinary total oestrogen and pregnanediol excretion and of plasma gonadotrophin and steroid levels under basal conditions and during dynamic tests (oestrogen provocation and LHRH‐tests). Results were compared to those obtained in a control group of regularly menstruating women, 23–45 years of age. Four different patterns of hypothalamic‐pituitary‐ovarian (H.P.O.) activity were identified in the perimenopausal subjects with DUB. In two patients with a history of persistent anovulation and cystic glandular hyperplasia of the endometrium, basal plasma gonadotrophin levels were normal but there was a failure to release an adequate amount of LH in response to endogenous and exogenous oestrogen stimulation. One subject had regular ovulatory cycles but the follicular phase was shorter and circulating levels of FSH, but not of LH, were higher than in controls. A similar monotropic increase in FSH was also present in a further patient whose cycles were irregular and included an ovulatory cycle with short follicular phase, an ovulatory cycle of normal length and an anovulatory cycle. In the remaining five women follicular development was infrequent and anovulation the rule. FSH and LH levels in these women were elevated despite the presence of circulating 17β‐oestradiol levels in the early‐mid follicular phase range. At the time of menopausal transition in one of these subjects, the decline of plasma 17β‐oestradiol to undetectable levels was associated with a further rise of both gonadotrophins. Conversely, following a prolonged period of follicular development with elevated urinary total oestrogen excretion in another subject, the raised gonadotrophin concentrations were suppressed and the pituitary response to LHRH was within the normal range. LHRH responses in the other four women were augmented. Oestrogen administration failed to induce a normal LH surge in three out of the five subjects. The results indicate that marked changes in the pattern of pituitary gonadotrophin secretion can be found in perimenopausal women with DUB. The observed increase in peripheral levels of FSH (with or without concomitant increase in LH) may be due to a change in hypothalamic‐pituitary sensitivity to the feedback effects of oestrogen. Alternatively, it is possible that these changes result from a decrease in the ovarian secretion of a hypothetical ‘inhibin‐like' substance produced by the growing follicle and for which the name ‘FSH‐release inhibiting substance’ (‘FRIS’) is proposed.
THE EFFECTS OF HALOTHANE ON PLASMA VASOPRESSIN DURING CARDIO‐PULMONARY BYPASS
Authors: SIMPSON PETER , FORSLING MARY
Published: March 2008

Plasma vasopressin concentrations were estimated in twelve patients undergoing cardio‐pulmonary bypass for open heart surgery. In six patients anaesthesia was maintained with 66% nitrous oxide in oxygen, whilst the remaining six additionally received halothane as a vasodilator during the bypass period. Induction of anaesthesia had little effect on plasma vasopressin concentrations, whilst marked increases were seen during surgery and bypass in both groups of patients. However, in those patients receiving halothane, significantly higher concentrations were reached, a maximum 36.1 ± 8.9 (SEM) μu/ml being seen in contrast to 15.4 ± 2.2 μu/ml in the group receiving nitrous oxide in oxygen alone.
EFFECT OF AMINOGLUTETHIMIDE ON URINARY CORTISOL AND CORTISOL METABOLITES IN ADOLESCENTS WITH CUSHING'S SYNDROME
Authors: ZACHMANN M. , GITZELMANN R. P. , ZAGALAK M. , PRADER A.
Published: March 2008

The effect of aminoglutethimide (AG) 4 × 250 mg (670 mg/m2 daily by mouth) on the excretion of free cortisol (radio‐immunoassay) and of its metabolites THE, THF‐alloTHF, cortolone and β‐cortolone (gas chromatography on capillary column) was studied monthly during 3 – 5 months in four adolescents (one girl, three boys) aged 15.9 – 18 years with Cushing's syndrome due to bilateral adrenal hyperplasia, but without evidence of a pituitary tumour.

Under AG, all compounds decreased to a minimum after 1 – 2 months. The decrease of THE‐ THF‐allo THF was most marked, followed by cortolone‐β‐cortolone and free cortisol. The sum of the conjugated metabolites was normalized, but free cortisol remained high. A rebound was noted after 3 – 5 months of continued treatment. This was associated with clinical relapse (weight gain, increasing blood pressure). With AG, a non‐steroidal peak appeared on the chromatograms.

It is concluded that: (1) AG is only temporarily effective in diminishing the excretion of cortisol and its metabolities; (2) paradoxical increments of 17‐ketosteroids as reported from colorimetric analysis are non‐specific and are probably due to the non‐steroidal peak; and (3) AG appears to modify steroid catabolizing liver enzymes (inhibition of 5β‐reductases and/or 3a‐dehydrogenase, possibly stimulation of 20a‐ and 20β‐dehydrogenases). This could increase the biological half‐life of cortisol and contribute to the clinical rebound, which is due to increased ACTH‐secretion.

Because of its excellent short‐term effects, AG appears to be useful to prepare patients for bilateral adrenalectomy.
SERUM TRIIODOTHYRONINE: CLINICAL EXPERIENCE WITH A NEW RADIOIMMUNOASSAY KIT
Authors: STEPANAS A. V. , MASHITER G. , MAISEY M. N.
Published: March 2008

A new kit for measuring total serum triiodothyronine (T3) by radioimmunoassay (‘T3 RIA’; Radiochemical Centre, Amersham) was evaluated using sera from 1114 patients and normal controls. The kit performed reliably with intraassay and inter‐assay variability figures of 3.9% and 9.3%, respectively, at‘medium’concentrations of T3. A T3 measurement could be obtained conveniently within 18 h after overnight incubation at room temperature. There were no critical steps dependent on time or temperature.

Serum T3 values showed no significant sex difference. There was no significant change in mean serum T3 between the ages of 15 and 69 years, but it fell by 0.15 nmol/1 for every 5 years beyond the age of 70. Mean serum T3 (±SD) for 335 normal euthyroid subjects aged 15 ‐69 years was 2.11 ±0.46 nmol/1 (range: mean±2 SD= 1.19‐3.03 nmol/1).

64% of pregnant euthyroid women and 12% of those taking oral contraceptives had elevated serum T3 levels, as did all hyperthyroid patients, apart from one with T4 toxicosis. Overlapping T3 values from hyperthyroid patients and euthyroid subjects with elevated concentrations of thyroid binding proteins could be separated completely by two correction techniques which related total serum T3 to the corresponding T3 resin uptake test, viz an‘augmented free T3 index, or a map plot of T3 vs T3 resin uptake. A 25% incidence of T3 toxicosis was observed. One hyperthyroid patient with T4 toxicosis, and seven euthyroid patients with‘biochemical T4 toxicosis’were investigated. 73% of moderately and 30% of severely hypothyroid patients had normal serum T3 levels. This overlap was not reduced by applying correction techniques.

Our studies demonstrate the value of serum T3 measurements in screening for and diagnosing hyperthyroidism. As T3 measurements become more widely available, it would seem reasonable to subclassify hyperthyroid patients into three types: those with‘T3/4 toxicosis, T3 toxicosis’and‘T4 toxicosis.
AN EVALUATION OF LABORATORY TESTS FOR THE DETECTION AND DIFFERENTIAL DIAGNOSIS OF CUSHING'S SYNDROME
Authors: HANKIN MARGARET E. , THEILE HELEN M. , STEINBECK A. W.
Published: March 2008

1. Results of tests for the diagnosis of Cushing's syndrome of various aetiologies are discussed for twenty‐five patients in whom the pathology was established by operation or autopsy.

2. Control values for the urinary excretion of free Cortisol, 17‐OHCS, Porter‐Silber chromogens (P‐SC) and 17‐OS and plasma levels of P‐SC are compared with those for normal subjects.

3. The results indicated that urinary values are within the normal range for some patients with Cushing's syndrome.

4. Plasma levels of P‐SC in the morning were within the normal range for the majority and elevated for the rest.

5. Some patients showed day‐night variation of plasma P‐SC but evening values were above the normal range.

6. The expected response for low dosage dexamethasone was found in all patients tested but unexpected responses followed high dosage in some.

7. Plasma 11‐OHCS in the five patients tested failed to respond to insulin induced hypoglycaemia.

8. Metyrapone administration and corticotrophin infusion tests had limited usefulness in establishing the aetiology of the disease. The 17‐OHCS excretion became raised in the response to corticotrophin and the elevation was prolonged beyond normal responsiveness.
THYROID‐STIMULATING IMMUNOGLOBULINS IN OPHTHALMIC GRAVES'DISEASE
Authors: TENG C. S. , SMITH B. REES , CLAYTON B. , EVERED D. C. , CLARK F. , HALL R.
Published: March 2008

Thyroid‐stimulating immunoglobulins (TSI) have been detected by receptor assay in the sera of 43% of patients with ophthalmic Graves’disease. Comparison of the receptor assay studies with thyroid function tests indicated that in several patients the antibodies detected by receptor assay were biologically inactive. In other patients, thyroid function appeared to be under TSI control with hyperthyroidism prevented by autoimmune destruction of the thyroid.
REDUCED‘GONADOTROPHS RESPONSE TO RELEASING HORMONE’AFTER CHRONIC ADMINISTRATION TO IMPOTENT MEN
Authors: DAVIES TERRY F. , GOMEZ‐PAN A. , WATSON M. J. , MOUNTJOY C. Q. , HANKER J. P. , BESSER G. M. , HALL REGINALD
Published: March 2008

Ten endocrinologically normal men with secondary sexual impotence were given 500 μg LHRH subcutaneously every 8 h. After 4 weeks treatment the LH response to 500 μg LHRH was reduced from a peak of 35.7 ± 5.2 to 16.8 ± 3.5 mu/ml (P< 0.01) and the FSH response from 4.2 ± 0.93 to 2.39 ± 0.4 mu/ml (P< 0.01). Circulating total testosterone, oestradiol, prolactin and sex hormone binding globulin showed no significant changes. Whether this inability of the pituitary to maintain its response to LHRH is peculiar to impotent men requires further study.
GLUCAGON AND DIABETES
Authors: PERRY‐KEENE D. A. , ALFORD. F. P. , CHISHOLM. D. J. , FINDLAY. D. M. , LARKINS R. G. , MARTIN F. I. R.
Published: March 2008

Clinical and biochemical variables were examined during two standardized, low‐dose insulin regimens in seven subjects with diabetic ketoacidosis and one with hyperosmolar coma, in order to determine whether glucagon levels can be suppressed in ketoacidosis and whether hyperglucagonaemia influences the clinical and biochemical responses to treatment. Glucagon concentrations were significantly elevated (36.6‐697.0 pmol/1) at presentation in all subjects. After institution of insulin treatment (4‐8 u/h), glucose and glucagon levels decreased rapidly, and in five of the eight subjects, glucagon levels reached undetectable concentrations (<3.0 pmol/1) during the initial treatment period. Further, neither plasma glucagon concentrations at presentation, nor the rate of glucagon decline during insulin treatment, appeared to influence the rapidity of the glucose decline or the persistence of the ketoacidosis. Thus, low‐dose exogenous insulin suppresses glucagon secretion in diabetic ketoacidosis, and the changes in glucagon concentrations during treatment are unrelated to the clinical response.
PHYSIOLOGIC SECRETION OF GROWTH HORMONE AND PROLACTIN IN MALE AND FEMALE RATS
Authors: TERRY LEON C. , SAUNDERS ADAH , AUDET JUDY , WILLOUGHBY JOHN O. , BRAZEAU PAUL , MARTIN JOSEPH B.
Published: March 2008

Growth hormone and prolactin are secreted episodically in man and experimental animals. To investigate physiologic mechanisms of GH and PRL secretion, a series of experiments were performed in individual, unanaesthetized male and female rats.

GH secretion in the male rat is characterized by intermittent surges that occur approximately every 3 h and are entrained to the light‐dark cycle. Peaks reach 200‐400 ng/ml and troughs are unmeasurable. PRL is secreted in more frequent episodes with a pattern distinct from GH.

In the female rat, GH surges occur more frequently‐approximately once each hour. PRL levels are low (<15 ng/ml) except on the afternoon of pro‐oestrous when they surge to levels of 100‐300 ng/ml. Prolactin rises 4‐6 h before delivery. Levels decline rapidly at the onset of parturition and surge with each episode of suckling in the post‐partum period. Growth hormone and corticosterone rise during delivery and remain elevated for several hours after delivery. Reinstitution of suckling after removal of pups causes an immediate rise in PRL and GH. The PRL response is sustained for 3‐4 h, whereas the GH response is brief with return to baseline within 1 h. The time courses of the two responses are clearly independent.

Stress in the male rat causes a rapid rise in PRL and suppression in GH. The PRL surge to stress is brief with return to baseline by 1 h. GH pulses are suppressed for up to 5 h after stress.

These studies indicate that separate neuroendocrine control mechanisms exist for regulation of the episodic release of GH and PRL in the rat.
IS THERE ANY ASSOCIATION BETWEEN THE PHARMACOLOGIC CONTROL OF PROLACTIN RELEASE AND ITS ACTION ON MAMMARY CARCINOGENESIS IN THE RAT?
Authors: FEUER G. , KELLEN J. A. , KOVACS K.
Published: March 2008

Pretreatment of female Wistar rats with various compounds (coumarin, 4‐methyl‐coumarin, phenobarbital, carbon tetrachloride) on mammary tumour production by 7,12 dimethylbenz(α)anthracene (DMBA) has been studied. The test compounds brought about a variety of actions on DMBA tumours; their effect varied from none (phenobarbital, carbon tetrachloride) to decreased incidence and delayed appearance (coumarin, 4‐methylcoumarin). In all cases studied increased prolactin level was found. The inhibitory action of coumarin on tumour incidence and multiplicity showed a dose‐related association with elevated serum prolactin and reduced hepatic drug metabolism.

These results indicate that the production of DMBA‐induced mammary adenocarcinomas in the rat is not associated with serum levels of prolactin. Our results suggest that in this model for tumorigenesis, prolactin only plays the role of a promoter after the carcinogenic event.
PREVENTION AND SUPPRESSION OF POST‐PARTUM LACTATION WITH 2‐BROMO‐ALPHA‐ERGOCRYPTINE (CB‐154)
Authors: MACLEOD S. C. , SCOTT J. , LORD L. , BRODIE G. , PERLIN I. , A.SIMPSON A.
Published: March 2008

Most clinical trials to date have demonstrated the effectiveness of 2‐bromo‐alpha‐ergocryptine in suppressing the onset of puerperal lactation and confirmed the postulative mechanism of action by suppression of serum prolactin concentrations during its administration. The present study involving 112 patients was carried out to demonstrate the dose response and the timing of the administration. The drug was administered in two dose schedules of 1 mg t.i.d. and 2.5 mg b.i.d. commencing immediately after delivery and continued for 14 days. A third group of patients had 2.5 mg administered b.i.d. only after acute engorgement became a problem in the post‐partum period. The drug was just as effective in the lower dose schedule and almost complete relief of pain and engorgement spared both the patient and the nursing staff many complaints. A dramatic relief was also obtained within 48 h even after engorgement had occurred and an overall incidence of rebound filling of 19% is similar to that reported by others.
FAILURE OF POSITIVE FEEDBACK IN NORMAL MEN AND SUBJECTS WITH TESTICULAR FEMINIZATION
Authors: VAN LOOK PAUL F. A. , HUNTER WILLIAM M. , CORKER CHARLES S. , BAIRD DAVID T.
Published: March 2008

The abdity of the hypothalamic‐pituitary unit to release luteinizing hormone (LH) in response to oestrogen Cpositive feedback) was studied in normal men and women and in subjects with testicular feminization or XY gonadal dysgenesis. Ethinyloestra‐diol (200 μg a day for 3 days) given orally to six regularly menstruating women during the early to mid follicular phase of the cycle evoked an LH surge which started between 48 and 72 h after the initiation of treatment. A similar positive feedback effect on the secretion of follicle‐stimulating hormone (FSH) could not be demonstrated.

In eight normal men there was no evidence for a stimulatory effect of ethinyl‐oestradiol (in doses of 200 μg or 500 μg a day for 3 days) on gonadotrophin release even though the levels of plasma ethyloestradiol in men on the higher dosage regime were greater than those found in women. Changes of peripheral LH, but not FSH, in men were inversely related to plasma ethinyloestradiol concentrations.

A patient with XY pure gonadal dysgenesis exhibited a female type of LH release in response to ethinyloestradiol administration (200 μg a day for 3 days), but two patients with the syndrome of testicular feminization failed to release LH.

The results suggest that normal adults of the two sexes differ in their ability to respond to ethinyloestradiol administration with LH release. The female response in XY gonadal dysgenesis emphasizes the importance of testicular secretions for the suppression of positive feedback whereas the male type of response in cases of testicular feminization indicates that testosterone does not represent the central mediator of this testicular function. The reported observations are compatible with the concept that the organizing action of the testes on positive feedback is mediated through 17β‐oestradiol.
THYROID FUNCTION IN NORMAL SUBJECTS IN ICELAND AND NORTHEAST SCOTLAND
Authors: HEDLEY A. J. , THJODLEIFSSON B. , DONALD D. , BECK J. SWANSON , CROOKS J. , CHESTERS M. I. , HALL R.
Published: March 2008

A comparative study was made of thyroid function in samples of‘well’subjects, from separate geographical areas with dissimilar dietary iodine levels. In the area with the higher iodine level, Iceland, the prevalence of positive thyroid antibody tests and serum thyrotrophm levels were lower, while the capacity of the thyroid to respond to exogenous thyrotrophin was higher than in NE Scotland, an ares with lower iodine levels. In contrast the prevalence of positive tests for another organ‐specific antibody, gastric parietal cell antibody, was higher in Iceland. These observations are consistent with the reported differences in the incidence rates for thyrotoxicosis and gastric carcinoma in the areas studied. The results are in agreement with our findings in two groups of post‐thyroidectomy patients from the same populations. This study provides support for the view that differences in the prevalence of constitutional and environmental factors in different populations contribute to the variation in reported outcome of treatment for thyroid disease.
RESPONSE TO THYROTROPHIN‐RELEASING HORMONE AND TRIIODOTHYRONINE SUPPRESSIBILITY IN EUTHYROID MULTINODULAR GOITRE
Authors: SMEULERS J. , DOCTER R. , VISSER T. J. , HENNEMANN G.
Published: March 2008

In twenty‐two female patients with euthyroid multinodular goitre of varying size, thyroid suppression of 1311 thyroid uptake by triiodothyronine (T3) and thyrotrophin (TSH) release after thyrotrophin‐releasing hormone (TRH) administration were compared with thyroid weight, estimated by a planimetric method, and with serum thyroxine (T4) and T3 concentrations. Maximal increment of TSH (ΔTSH) after TRH and per cent T3‐suppressibihty were inversely related to thyroid weight and not related to basal serum T4 or T3 concentrations. ΔTSH and per cent suppression correlated positively, but ΔTSH was more often subnormal than T3‐suppressibihty. A practical consequence of our study is that nonconformity of the two tests may occur. This should be kept in mind in the evaluation of patients with thyroid disorders.
VITAMIN D METABOLISM
Authors: DELUCA HECTOR F.
Published: March 2008

During the past decade, an explosion of information has become avdable on the metabolism and function of vitamin D whch is of great importance to clinicians in the treatment of metabolic bone disease. We have learned that vitamin D is the precursor of at least one hormone and that ths hormone carries out functions in calcium and phosphorus metabolism brmging about mineralization of bone on one hand, and the prevention of hypocalcaemic tetany on the other. It may also function in the prevention of such degenerative bone diseases as osteoporosis. An important analogue of this hormone, lα‐hydroxyvitamin D3 has been prepared and is used successfully in the treatment of a variety of clinical conditions. This presentation will summarize these findings and their possible implications in these metabolic bone diseases.
BONE HISTOMORPHOMETRY IN PATIENTS WITH CHRONIC RENAL FAILURE: EFFECT OF 1α‐HYDROXYVITAMIN D3
Authors: MELSEN F. , NIELSEN H. E. , CHRISTENSEN M. S.
Published: March 2008

Morphometric and dynamic studies of iliac crest bone biopsies were carried out in twelve patients with chronic renal failure (six on chronic haemodialysis and six with renal insufficiency) before and after 6 montsh of lα‐hydroxyvitamin D3 treatment. Pre‐treatment biopsies showed signs of osteomalacia and hyperparathyroidism. Biopsies taken during treatment showed changes towards normality, indicating a beneficial effect of lα‐hydroxyvitamin D3.
CORRELATION OF CLINICAL, BIOCHEMICAL AND SKELETAL RESPONSES TO l α ‐HYDROXYVITAMIN D3 IN RENAL BONE DISEASE
Authors: KANIS J. A. , EARNSHAW M. , HENDERSON R. G. , HEYNEN G. , LEDINGHAM J. G. G. , NAIK R. B. , OLIVER D. O. , RUSSELL R. G. G. , SMITH R. , WILKINSON R. H. , WOODS C. G.
Published: March 2008

Thirty‐five patients with bone disease and chronic renal failure (twenty‐four on maintenance haemodialysis) were treated for 7–39 months with lα‐hydroxyvitamin D3, 2–25 μg daily by mouth. Symptoms (bone pain and muscle weakness) and radiographic appearances improved and plasma alkaline phosphatase returned to normal in the majority of patients (87, 76 and 75% respectively). In contrast, histological appearances in bone improved in only 46% twenty‐three patients from whom paired biopsies were available, and this change was not greatly different from that seen in a comparable group of untreated patients. Significant correlations were noted in individual patients between the changes in symptoms, X‐rays, plasma alkaline phosphatase and immunoreactive parathyroid hormone and these, in turn, were related to histological changes in bone, although these latter changes were often small. It is concluded that lα‐hydroxyvitamin D3 is a useful new drug in the treatment of renal bone disease, but that the evaluation of the response depends critically on the method of assessment used.
EFFECT OF lα‐HYDROXYVITAMIN D3 ON PARATHYROID FUNCTION IN PATIENTS WITH CHRONIC RENAL FAILURE
Authors: NIELSEN H. E. , CHRISTENSEN M. S. , MELSEN F. , RØMER F. K. , HANSEN H. E.
Published: March 2008

The effect of lα‐hydroxyvitamin D3 (1α‐OHD3) on parathyroid function was studied in sixteen patients (ten on haemodialysis, six with chronic renal insufficiency) during treatment for 6–8 months.

During treatment, a decrease in serum parathyroid hormone (s‐PTH) and an increase in serum calcium were seen. An inverse linear correlation was found between serum calcium and logarithmic values of s‐PTH in fifteen of sixteen patients, but the slopes of the regression lines varied considerably. This indicates that the suppression of parathyroid function seen during treatment with lα‐OHD3 is mediated by a rise in the serum concentration of calcium. For normalization of s‐PTH, the serum concentration of calcium had to be above normal range in several patients, indicating a defect in calcium‐mediated regulation of the secretion of parathyroid hormone. Tlus abnormality was seen especially in long‐term haemodialysed patients.
THE EFFECT OF lα‐HYDROXYVITAMIN D3 IN PRE‐DIALYSIS RENAL BONE DISEASE
Authors: PIERIDES A. M. , ELLIS H. A. , SIMPSON W. , COOK D. , KERR D. N. S.
Published: March 2008

Assessment of 18 azotaemic patients treated with long‐term 1 a‐hydroxyvitamin D, (lα‐OHD3) confirms the generally favourable effect of this analogue of 1,25‐dihydroxyvitamin D3 in azotaemic osteodystrophy. Growing chddren with radiological rickets respond very well as do adults showing mild hyperpara‐thyroidism with or without osteomalacia. However, patients with severe‘pure’hyperparathyroidism and features of autonomy do not respond well and in such patients lα‐OHD3 alone should be avoided. Phosphate restriction and occasionally a sub‐total parathyroidectomy may be indicated in these patients.
MEASUREMENT OF WHOLE BODY CALCIUM IN CHRONIC RENAL FAILURE: EFFECTS OF lα‐HYDROXYVITAMIN D3 AND PARATHYROIDECTOMY
Authors: NAIK R. B. , DABEK J. T. , HEYNEN G. , JAMES H. M. , KANIS J. A. , ROBERTSON P. W. , ROBINSON B. H. B. , WOODS C. G.
Published: March 2008

In vivo neutron activation analysis was used to measure changes in whole body calcium in patients with chronic renal failure. Eight patients, not treated by haemodialysis, showed losses of calcium in contrast to increases noted in twenty‐one patients treated by haemodialysis. Changes in whole body calcium were independent of preexisting renal bone disease. Treatment of bone disease by total parathyroidectomy (six patients) or lα‐hydroxy vitamin D3 (eleven patients) resulted in large increases in total body calcium. In patients given lα‐hydroxy vitamin D3, changes in total body calcium correlated with hstological and radiological indices of response but variable changes in forearm bone mineral content were observed. Neutron activation analysis provides a convenient method for measuring skeletal mass and may also be useful in the assessment of response to lα‐hydroxyvitamin D3 of patients with osteitis fibrosa and osteomalacia.
PHYSIOLOGICAL AND THERAPEUTIC DIFFERENCES BETWEEN VITAMIN D, ITS METABOLITES AND ANALOGUES
Authors: KANIS J. A. , RUSSELL R. G. G. , SMITH R.
Published: March 2008

Since several metabolites and analogues of vitamin D have become available, their physiological and therapeutic potential have been studied in various disorders of mineral metabolism, particularly those classically termed vitamin D‐resistant. In some instances this resistance appears to be due to defective metabolism of vitamin D or to defective target organ responses. but in others it is not. Although the precise effect of vitamin D or its metabolites on mineralization of bone is still unknown there is some evidence that the metabolites differ in their relative effects on intestine, bone, muscle and parathyroid glands. These differences may eventually have therapeutic value. At present the major advantage of lα‐hydroxylated derivatives of vitamin D over other compounds resides in their more rapid onset and reversal of action which makes them much easier and safer to use.
THE MANAGEMENT OF H Y POP A R ATH YRO ID ISM WITH lα‐HYDROXYVITAMIN D3
Authors: HEYBURN P. J. , PEACOCK M.
Published: March 2008

A retrospective study of the comparative effects of vitamin D, dihydrotachysterol and lα‐hydroxy vitamin D3 was undertaken in twentyeight patients with hypo‐parathyroidism. The vitamin D compounds restored plasma calcium to the normal range in most patients with comparable actions on the gut, bone and Kidney. Although the vitamin D compounds had a direct action on kidney and bone in the absence of PTH, the major action in maintaining plasma calcium was on the gut. Plasma phosphate fell due to a reduction in renal tubular reabsorption. Dihydrotachysterol and lα‐hydroxyvitamin D3 had significant practical advantages over vitamin D in their rapid onset of action and their relatively short biological half–life.
VITAMIN D RESISTANT HYPOPHOSPHATAEMIC OSTEOMALACIA: TREATMENT WITH la–HYDROXYVITAMIN D3
Authors: PEACOCK M. , HEYBURN P. J. , AARON J. E.
Published: March 2008

Ten patients with vitamin D resistant hypophosphataemic osteomalacia are described. They had hypophosphataemia with a decreased tubular reabsorption of phosphate, malabsorption of calcium and phosphorus, proximal myopathy and extensive osteomdacic changes on iliac crest bone biopsy. The plasma alkaline phosphatase and urine hydroxyproline, however, were raised in only some of the patients. Treatment with l a–hydroxyvitamin D3 in high doses rapidly cured the myopathy, increased calcium and phosphorus absorption and retention and healed the osteomalacia. Phosphorus supplements were not required.
METERGOLINE INHIBITION OF THYROTROPHIN AND PROLACTIN SECRETIONS IN PRIMARY HYPOTHYROIDISM
Authors: DELITALA G. , ROVASIO P. P. , MASALA A. , ALAGNA S. , DEVILLA L.
Published: March 2008

The effect of acute oral administration of metergoline on serum thyrotrophin and prolactin levels in six patients with primary hypothyroidism was studied. Metergoline 4mg by mouth caused a significant decrease in the concentration of serum thyrotrophin and prolactin in all subjects. There was no consistent change in serum thyroxine and triiodothyronine concentrations during the experiment. These findings suggest that metergoline inhibits prolactin and thyrotrophin secretion by a direct action on the hypothalamus or pituitary gland.
THYROID FUNCTION TESTS IN PATIENTS ON LONG‐TERM TREATMENT WITH VARIOUS ANTICONVULSANT DRUGS
Authors: LIEWENDAHL K. , MAJURI H. , HELENIUS TUULA
Published: March 2008

Thyroid function tests were studied in patients undergoing long‐term treatment with various anticonvulsant drugs. Previous reports that diphenylhydantoin induces a decrease in the serum concentrations of total and free thyroxine (T4) and tri‐iodothyronine (T3) without a change in the TSH concentration were confirmed. Diphenylhydantoin had no effect on reverse T3. Carbamazepine was also found to decrease serum T4, the free T4 index and T3 but, with the exception of T3, the decrease was smaller than that induced by diphenylhydantoin. Dipropylacetic acid did not influence the serum thyroid hormone concentrations, and neither did primidone. This demonstrates that the interaction between anticonvulsant drugs of different chemical structure and thyroid hormone metabolism is diverse. None of the drugs tested altered serum TSH or the T3 uptake test for the estimation of unsaturated thyroid hormone binding‐capacity in serum. These two tests are considered diagnostically more dependable than the measurement of thyroid hormones in serum when diphenylhydantoin and carbamazepine are administered.
PLASMA INSULIN DISAPPEARANCE CURVE AFTER INTRAVENOUS INSULIN INJECTION IN HUMAN HYPERTHYROIDISM
Authors: WAJCHENBERG BERNARDO LÉO , CESAR FERNANDO PRESTES , LEME CARLOS EDUARDO , DIDIO RENATO , KIEFFER JÚLIO
Published: March 2008

The disappearance curves of plasma insulin after intravenous injection of unlabelled pork insulin was studied in nine young female hyperthyroid subjects with Graves’ disease and eleven young female normal subjects, who served as controls. Comparison of the curves by analysis of variance did not reveal statistical differences between them (Fobtained= 2.8, F0.05= 4.41), implying that there was no significant differences in the transference of injected insulin from plasma to the extra‐vascular space between hyper‐ and euthyroid subjects. The results may suggest that the metabolism of insulin is not appreciably affected in hyperthyroidism.
RESPONSE TO THYROTROPHIN RELEASING HORMONE IN KLINEFELTER'S SYNDROME
Authors: YAP P. L. , RENTON W. B. , PRICE W. H. , FYFFE J. A. , LIDGARD G. P.
Published: March 2008

In eleven patients with Klinefelter's Syndrome TSH, T4 and T3 levels have been measured after stimulation with TRH. The eleven patients included three who had been noted to have a low radioactive iodine uptake and two of these also had abnormally low T4 levels. Three of the patients were receiving androgen replacement therapy. A normal response to TRH was observed in all cases.
AUTONOMY IN EUTHYROID GOITRE: MALADAPTATION TO IODINE DEFICIENCY
Authors: EMRICH DIETER , BÁHRE MARTIN
Published: March 2008

The occurrence of negative TRH tests in euthyroid goitre was analysed in 486 patients without scintigraphic evidence of autonomous adenoma from an area of iodine deficiency. After ensuring by various means that methodological errors could be excluded, the following results were obtained.

(1) The overall frequency of a negative TRH test was 15%. It increased with age of the patients, the weight of the goitre and the existence of non‐homogenity in the thyroid scan. Sex, contraceptive drugs and treatment for reduction of the goitre did not influence the number of negative TRH tests. But previous iodine medication led to a significant increase accompanied by an increase of the mean FT4 index.

(2) Although in the normal range, the mean concentration of T4 and T3 in non‐premedicated TRH‐negative patients was significantly higher compared to positive ones.

(3) The suppression test in patients with a negative TRH test was negative in 40% of them. These patients had higher mean values of T4 and T3 compared to those who did suppress.

In connection with the findings of Miller & Block (1970) who demonstrated autonomous microscopic areas in euthyroid goitres, an hypothesis is presented that, in a certain number of iodine deficient goitres, a transition takes place from adaption through TSH‐induced hypertrophy to adaption through autonomy.
THYROID HORMONE, OESTROGEN, AND GLUCOCORTICOID EFFECTS ON TWO DIFFERENT PITUITARY GLYCOPROTEIN HORMONE ALPHA SUBUNIT POOLS
Authors: KOURIDES IONE A. , WEINTRAUB BRUCE D. , RE RICHARD N. , RIDGWAY E. CHESTER , MALOOF FARAHE
Published: March 2008

Seven hypothyroid women (six postmenopausal and one premenopausal) were treated with 200 or 300 μg of levo‐T4 daily in order to suppress the secretion of TSH and its alpha and beta subunits. After such therapy, serum TSH and beta subunit of TSH (TSH‐β) levels were usually not detectable. Serum alpha decreased from a mean value of 4.5 ± 0.8 ng/ml to 2.8 ± 0.4 ng/ml (P > 0.01). Serum LH and FSH levels were unchanged. Oestrogen administration (20 mg diethylstilboestrol daily for 3 or 5 days) to these patients further decreased mean serum alpha to 1.9 ± 0.2 ng/ml (P > 0.005). In addition serum LH, FSH, and the beta subunits of LH and FSH decreased with oestrogen treatment. In separate experiments glucocorticoids (dexamethasone 4 mg every 6 hours for 10 doses) were administered to eight normal individuals, four women with decreased thyroid reserve, and one hyper‐thyroid woman. Not only did basal and TRH‐stimulated TSH secretion decrease, but secretion of alpha and TSH‐β also decreased after dexamethasone administration, with the largest fall in the patients with decreased thyroid reserve. The change in these thirteen patients’ alpha subunit increment after TRH administration was from a mean of 1.6 to 1.0 ng/ml with glucocorticoids; the change in TSH‐β was from a mean of 1.1 to 0.7 ng/ml. Serum LH and FSH concentrations were not altered by glucocorticoid administration. These studies have demonstrated two different pools of alpha subunits in the pituitary gland. Thyroid hormone and glucocorticoids decreased secretion of alpha subunits arising from the thyrotroph; oestrogen decreased secretion of alpha subunits arising from the gonadotroph.
GROWTH HORMONE MODULATION OF ARGININE‐INDUCED GLUCAGON RELEASE: STUDIES OF ISOLATED GROWTH HORMONE DEFICIENCY AND ACROMEGALY
Authors: SEINO YUTAKA , TAMINATO TOMOHIKO , GOTO YASUO , INOUE YOSHIMICHI , KADOWAKI SEIZO , HATTORI MASAHIRO , MORI KOZABURO , KATO YUZURU , MATSUKURA SHIGERU , IMURA HIROO
Published: March 2008

Plasma glucagon and insulin responses to l‐arginine were compared in normal controls and patients with isolated growth hormone deficiency and acromegaly. Patients with isolated growth hormone deficiency were characterized by high plasma glucagon response and low plasma insulin response, whereas acromegalic patients showed exaggerated plasma glucagon response and almost normal insulin response. These results suggest that growth hormone is probably required for optimum function of the islets, and since hyperglucagonaemia was observed in both growth hormone deficiency and acromegaly, metabolic disturbances stemming from the respective primary diseases may affect glucagon secretion.
PLASMA ACTH AND CORTISOL PROFILES IN ADDISONIAN PATIENTS RECEIVING CONVENTIONAL SUBSTITUTION THERAPY
Authors: SCOTT R. S. , DONALD R. A. , ESPINER E. A.
Published: March 2008

Plasma ACTH and cortisol profiles were studied over 24 h in five Addisonian patients maintained in good health by conventional gluco‐ and mineralocorticoid treatment. Patients received their usual treatment (15–30 mg cortisol daily) in divided doses at 08.00 and 16.00 hours. Plasma cortisol concentrations differed from those of control subjects in being higher from 08.00 hours‐noon and 17.00–18.00 hours and were unmeasurable (>20 nmol/l) during the period of active cortisol secretion (03.00–08.00 hours) observed in normal subjects. Peak plasma ACTH levels (618‐>1600 ng/l) occurred at 08.00–09.00 hours in the Addisonian patients and were much greater than those seen in control subjects (60–220 ng/l). Despite this, plasma ACTH fell promptly within 3 h of the morning dose to less than 100 ng/l and levels were indistinguishable from those seen in normal subjects over the period 12.00–02.00 hours. These results show that there are substantial differences between treated Addisonian and control subjects in respect of plasma cortisol and ACTH concentrations. The findings may lead to a better understanding of ACTH‐cortisol relationships in disease states, including congenital adrenal hyperplasia where control of excessive ACTH secretion is clinically desirable.
RETURN OF OVARIAN FUNCTION AFTER ABORTION
Authors: LÄHTEENMÄKI P. , LUUKKAINEN T.
Published: March 2008

The first menstrual cycle after a therapeutic abortion was studied in eighteen women by measuring plasma oestradiol and progesterone concentrations and the urinary excretion of LH until the first menstruation.

The plasma concentrations of oestradiol and progesterone declined rapidly, reaching low values as early as the second day after the abortion. An increase in plasma oestradiol levels was observed from the seventh post‐abortal day onwards. A peak of short duration in the plasma progesterone concentrations occurred during the increased oestradiol synthesis.

The concentration of progesterone during the luteal phase of the cycle was lower than in a normal cycle, indicating an inadequate luteal function. Return of ovulation was observed in 83% of patients during the first cycle; as judged by a biphasic oestradiol profile in plasma, a mid‐cycle LH peak, and subsequent elevation of progesterone. The first LH peak was observed 16 days after the abortion.

The rapid return of the ovulatory function makes immediate post‐abortal contraception a necessity.
IS THE ‘SODIUM INDEX’ A USEFUL WAY OF EXPRESSING CLINICAL PLASMA RENIN, ANGIOTENSIN AND ALDOSTERONE VALUES?
Authors: ROSEI E. AGABITI , BROWN J. J. , CUMMING ALISON M. M. , FRASER R. , SEMPLE P. F. , LEVER A. F. , MORTON J. J. , ROBERTSON A. S. , ROBERTSON J. I. S. , TREE M.
Published: March 2008

In normal subjects taking variously high, normal or low sodium diets, while potassium intake was maintained within the normal range, highly significant inverse relationships were demonstrated between 24 h urinary sodium output and the concurrent plasma concentrations of renin, angiotensin II and aldosterone. With linear coordinates, these relationships were described by rectangular hyperbolae. With logarithmic plots the relationships became rectilinear. When 24 h urinary sodium output was 75 mmol or higher, there was no worthwhile advantage in relating renin to sodium excretion; plasma angiotensin II and aldosterone, however, were significantly related inversely to urinary sodium in this range. When 24 h urinary sodium output was below 10 mmol, plasma renin, angjotensin II and aldosterone all varied over wide but elevated ranges and were not significantly related to urinary sodium excretion rates. We conclude that whereas estimations of urinary sodium may be of value in revealing latent aberrations of sodium intake, there is no distinct advantage in relating measurements of renin or angiotensin II to urinary sodium output if the diet is known to be within broad ‘normal’ limits. This should simplify the relevant blood sampling procedure under both ward and outpatient conditions. If plasma renin, angiotensin II and aldosterone are to be related to concurrent urinary sodium output, logarithmic, rather than linear, co‐ordinates, are appropriate.
GROWTH RETARDATION, SKELETAL MATURATION AND THYROID FUNCTION IN CHILDREN WITH HOMOZYGOUS β‐THALASSAEMIA
Authors: MADEDDU G. , DORE A. , MARONGIU A. , LANGER‐COSTANZI M.
Published: March 2008

Growth rate, skeletal maturation and thyroid function were measured in fifty thalas‐saemic children (age 2–13 years) and in fifty controls (matched for sex and age who were not anaemic. Growth retardation was present in several patients during the first years of life and affected almost all subjects examined when they were approaching puberty. Discrepancy between bone and height age in patients was not significantly different from controls. The finding of low T4 and T3 with a high TSH indicated thyroid hypofunction. This finding, already present early in life, did not worsen with increasing age. In β‐thalassaemia hypothyroidism cannot be the cause of retarded growth since there is no relationship between the impairment in thyroid function and severity of growth retardation. In addition, height age was not different from bone age, while a discrepancy is a constant feature of low stature due to hypothyroidism.
A COMPARISON OF THE EFFECTS OF CLOMIPHENE AND TAMOXIFEN TREATMENT ON THE CONCENTRATIONS OF OESTRADIOL AND PROGESTERONE IN THE PERIPHERAL PLASMA OF INFERTILE WOMEN
Authors: SENIOR B. E. , CAWOOD MARION L. , OAKEY R. E. , MCKIDDIE J. M. , SIDDLE D. R.
Published: March 2008

The effects of clomiphene and tamoxifen treatment on the concentrations of oestradiol and progesterone in plasma were compared in the same infertile women. Nine patients, three with anovulation and six with suspected luteal phase deficiency, were given clomiphene during 2 months and tamoxifen during 2 months. Placebo treatment was given in the month before the first drug and during a month between drug treatments. The concentrations of oestradiol and progesterone were determined by radioimmunoassay in three samples collected each month between days 6 and 8, 11 and 13, and 18 and 20.

The mean concentration of oestradiol at the time of the expected pre‐ovulatory rise was 0.82 nmol/l with placebo treatment, 1.20 nmol/l following tamoxifen treatment and 5.00 nmol/l after clomiphene treatment (normal menstrual cycle maximum, 2.0 nmol/l). The mean concentration of progesterone in the luteal phases reached maxima of 41 nmol/l, 47 nmol/l and >72 nmol/l, respectively (normal menstrual cycle maximum, 60 nmol/l). When the frequency distributions of hormone concentrations were examined for each treatment, clomiphene and tamoxifen were both found to alter the distribution from that of placebo treatment (Chi‐square analysis), giving a larger proportion of high concentrations.

In the six patients with suspected luteal phase deficiency clomiphene treatment was followed by biochemical evidence of ovarian hyperstimulation. There was no evidence of this when any of these patients were treated with tamoxifen, nor in anovulatory patients treated with clomiphene.
INFLUENCE OF HYPERPROLACTINAEMIA DUE TO METOCLOPRAMIDE ON GONADAL FUNCTION IN MEN
Authors: FALASCHI P. , FRAJESE G. , SCIARRA F. , ROCCO A. , CONTI C.
Published: March 2008

Five clinically normal male volunteers were given metoclopramide, 10 mg t.d.s. for 6 weeks. During treatment prolactin concentrations were elevated (over 50 ng/ml) in all. LH, FSH, testosterone and cortisol concentrations were not altered. No change was observed in LH or FSH responses to LHRH testing 4 weeks after the beginning of therapy, compared with pre‐treatment values. A reduction in seminal volume and total sperm count were observed in each subject. Four noticed a decrease in libido and three lost spontaneous erections. While the metoclopramide‐induced hyperprolactinaemia could be the cause of the observed changes in semen and erectile activity, it is possible that this dopamine receptor blocking drug might directly affect central or peripheral mechanism of erection, the testes or accessory organs.
A LOW T3 SYNDROME IN DIABETIC KETOACIDOSIS
Authors: NAEIJE R. , GOLSTEIN J. , CLUMECK N. , MEINHOLD H. , WENZEL K. W. , VANHAELST L.
Published: March 2008

The pituitary‐thyroid axis was investigated in nineteen euthyroid patients with severe diabetic ketoacidosis. A ‘low T3 syndrome’ was found, with the following characteristics: lowered serum concentrations of triiodothyronine (T3), increased reverse triiodothyronine (rT3), slightly low thyroxine (T4), normal thyrotrophin (TSH), slightly increased triiodothyronine uptake (RT3U) values, and a blunted TSH response to thyrotrophin‐releasing hormone (TRH). These disturbances in thyroid‐function tests required several days good control of the diabetes to be corrected, at least partially. The data suggest the presence of an abnormal extrathyroidal T4 metabolism as well as a pituitary defect. Caution is recommended in the interpretation of thyroid‐function tests during and several days after the treatment of diabetic ketoacidosis.