Outpatient management of patients with large multinodular goitres treated with fractionated radioiodine.

The efficacy of fractionated out-patient radioiodine therapy in 38 patients with compressive symptoms due to long-standing large multinodular goitres was assessed. The diagnosis was established by clinical assessment in addition to technetium-99m pertechnetate thyroid scan or computed tomography scan of the thyroid and mediastinum. Oral iodine-131 therapy was administered as a 2.22 GBq (60 mCi) cumulative dose over 4 months (555 MBq per month). All patients were monitored with serum thyroid-stimulating hormone and free thyroxine (+/- free tri-iodothyronine) assays before the treatment and after each dose fraction. Clinical and biochemical follow-up was performed on all patients and ranged from 6 to 45 months after therapy. The patients consisted of 35 female and three male patients with a median age of 59 years (range 37-87 years). Prior to treatment 20 patients were biochemically hyperthyroid and 18 were euthyroid. Overall, 71% of patients reported a subjective improvement in compressive symptoms and 29% reported no change. Clinically assessed reduction in goitre size occurred in 92% of patients while there was no change in 8%. At 3 months of follow-up, 31% of patients had become hypothyroid and at 18 months 66% were hypothyroid. Seven hyperthyroid patients (35%) became euthyroid and 13 hyperthyroid patients (65%) became hypothyroid. Three patients who became hypothyroid experienced neck soreness (transient in one patient, persistent in two patients). There were no differences in outcome between patients who were hyperthyroid and those who were euthyroid prior to treatment. Fractionated out-patient radioiodine therapy showed excellent short- and medium-term safety, was very well tolerated and offered a satisfactory alternative treatment to surgery.

Effect of calcitonin on hemodialysis patients with hypercalcemia and renal osteodystrophy.

Because calcitonin administration has been shown to decrease the serum calcium level in certain hypercalcemic conditions, 10 patients on maintenance dialysis with renal osteodystrophy and persistent hypercalcemia were treated with salmon calcitonin for 3 months. While plasma calcium concentrations were reduced by calcitonin therapy in four patients, therapy was ceased in two patients due to a worsening of their hypercalcemia, although in another two patients the initial worsening of the hypercalcemia settled with continued therapy. No significant changes in calcium levels occurred in the remaining two patients. Analysis of the data suggests that a hypocalcemic effect of calcitonin was most likely in the presence of osteomalacia, while predominant osteitis fibrosa favored a hypercalcemic response. Calcitonin administration caused a mean increase in parathyroid hormone (PTH) secretion 3.6 +/- 1.5 to 6.5 +/- 1.7 ng/ml; p less than 0.05) after 6 weeks of therapy. Three patients reported improvement in their bone pain. These studies show that despite possible symptomatic and morphological effects of calcitonin, its hypocalcemic effect in patients with renal osteodystrophy and hypercalcemia is inconsistent.

Licorice raises urinary cortisol in man.

The finding that urine cortisol excretion was increased in patients with hypokalaemic hypertension induced by licorice addiction led to this study on the effect of licorice in normal subjects. Thirteen normal volunteers ate either 100 or 200 g licorice for 1-4 weeks and assessment of pituitary-adrenal function was made before, during, and 1 week after cessation of licorice ingestion. Urine cortisol excretion more than doubled in 10 of 13 subjects (mean, 33.8 +/- 15.6 SD before and 83.3 +/- 56 SD micrograms/24 h at 1 week after commencing licorice) and excretion rates similar to those observed in Cushing's syndrome were seen in 7 subjects (range, 91-226, compared to normal range of 11-82 micrograms/24 h). Urine cortisol excretion remained significantly elevated (P less than 0.01) above control levels for at least 1 week after licorice was withdrawn. Despite these increases, urinary steroid metabolite (tetrahydrocortisol, tetrahydrocortisone, tetrahydro-11-deoxycortisol, 17-ketogenicsteroids, and 17-ketosteroids) excretion was not affected, plasma cortisol and ACTH values were unchanged, and normal 0800-1600-h diurnal variation of plasma cortisol was maintained. The direct intraadrenal infusion of the active mineralocorticoid component of licorice, glycyrrhetinic acid, in two sheep with autotransplanted adrenal glands failed to stimulate cortisol secretion acutely. It is concluded from these studies that the licorice-induced changes in cortisol excretion are not a result of adrenocoritcal stimulation but more likely represent a change in the renal handling of cortisol.

Effect of eating liquorice on the renin-angiotensin aldosterone axis in normal subjects.

The effect of confectionery liquorice on electrolyte status and the renin-angiotensin-aldosterone (RAA) axis was studied in 14 healthy volunteers. They ate liquorice in daily doses of 100 g or 200 g (equivalent to 0-7-1-4 g glycyrrhizinic acid) for one to four weeks. Plasma potassium concentrations fell by over 0-3 mmol/l in 11 people, including four who had to be withdrawn from the study because of hypokalaemia. One or more values of the RAA axis, especially plasma renin activity and urinary aldosterone concentrations, were considerably depressed in all subjects. These results show that potentially serious metabolic effects may occur in some people who eat modest amounts of liquorice daily for less than a week.

Plasma testosterone and prolactin in the menstrual cycle.

Daily hormonal studies during nine ovulatory menstrual cycles showed that plasma prolactin and testosterone concentrations fluctuated randomly and independently. Mean plasma testosterone levels were found to be higher during the 7 days before and after the mid-cycle LH peak when compared to the premenstrual phase (P less than 0-01). No correlation was found between daily levels of prolactin and those of LH, FSH, oestrogen or progesterone and no correlation was seen between peaks of prolactin and testosterone or mean prolactin and testosterone levels. The lack of correlation between blood levels of prolactin and testosterone during the menstrual cycle suggests that prolactin is unlikely to have any direct controlling influence on the cyclical nature of testosterone production observed during ovulatory menstrual cycles.

Migraine and reporoductive hormones throughout the menstrual cycle.

In a clinical survey the relation between migraine and menstruation was studied in 142 otherwise healthy women. In 24, onset of migraine coincided with the year of menarch. Of the 138 patients in whom onset of migraine predated the menopause, there were only 13 in whom attacks occurred regularly, and only, just before or during menstruation; in a further 11 attacks occurred regularly in relation to menstruation and at other times. Those with menstrually related migraine were more likely to have onset of migraine at menarche, to have associated weight gain and breast discomfort as part of a periodic syndrome, and to show improvement during pregnancy. There appeared no clear pattern of change at the menopause. In a study of reproductive hormones, blood was collected daily throughout a menstrual cycle from each of 8 women with menstrually related migraine, 6 with menstrually non-related migraine, and 8 healthy headache-free controls. Plasma levels of follicle-stimulating hormone (F.S.H.), luteinising hormone (L.H.), prolactin, oestrogen, and progesterone were measured in all. Plasma-testosterone was measured in 8 migraine patients. Mean plasma oestrogen and progesterone levels were significantly higher in migraine patients than controls for most of the menstrual cycle, with the most striking differences found in the late luteal phase for progesterone. No significant difference was found between the menstrually related and non-related patients for these or the other hormones measured. Mean plasma-prolactin levels were lower in migraine subjects than controls, but the difference was not significant. Mean plasma F.S.H. and L.H. levels were similar in both migraine and control groups. Plasma-testosterone levels were within the range for normal in the 8 migraine patients studied. No specific hormone changes were associated with the occurrence of a migraine attack, nor did rising or falling levels, or greater increments of change over given cycle phases, appear important in provoking attacks.

Plasma gonadotropins and androgens in surgically treated cryptorchid patients.

Plasma LH, FSH, and total 17betaOH androgen levels were measured in a group of 40 adult patients who underwent orchiopexy for either unilateral or bilateral cryptorchism during childhood. Gonadotropin abnormalities were found in 15 of 40 patients and thereby appeared to be a much more sensitive indicator of testicular malfunction than the androgens which were abnormal in only four patients. In the postpubertal phase, the estimation of gonadotropins and androgens appeared valuable, first, as an additional help in the prognosis of fertility, where combined raised levels of LH and FSH were found to indicate a poor prognosis; second, to detect in infertile patients gonadotropin deficiency which, if previously missed, can still be expected to respond to gonadotropin therapy; third, for the detection of the subclinically hypogonad group who may require follow-up, and finally for the detection of the low-androgen group who may require some form of hormonal therapy. As several patients in this study were found to have low gonadotropins, it is postulated that low levels of gonadotropin may play a role in the production of cryptorchism. The finding of high gonadotropin levels in another group may indicate a feedback mechanism sensitive to a damaged testis, but alternatively it is possible that there might be a primary resistance to the action of gonadotropins and it is postulated that such a resistance may be an additional factor of the causation of cryptorchism in some cases.