Isolated follicle-stimulating hormone deficiency in men: successful long-term gonadotropin therapy.

Two men with primary infertility after 6 to 11 years of marriage were found to have isolated follicle-stimulating hormone deficiency syndrome (IFDS). Their endogenous gonadotropin secretion was compared with that of two other infertile men with hypothalamic disease (Kallmann's syndrome) and pituitary tumor with hyperprolactinemia. Treatment with intramuscular gonadotropin was given to produce circulating and 24-hour urine levels of luteinizing hormone and follicle-stimulating hormone at or above the upper limit of the normal male range to ensure continued gonadal stimulation. Sperm counts increased in IFDS men within 6 to 26 weeks, with maximum total sperm counts of 33.5 and 20 million after 9 to 80 weeks. Pregnancy occurred after 20 weeks' therapy in one patient's wife with the subsequent delivery of a normal male infant. IFDS may be a treatable cause of male infertility given adequate gonadotropin therapy.

The unit area trichogram in the assessment of androgen-dependent alopecia.

The unit area trichogram was defined in the frontal and occipital areas of ten normal men and ten normal women and the results compared with the findings in ten male and fifteen female patients with androgenic alopecia. The epilation technique provided accurate data of normal hair density (higher than previously reported) and the phases of hair growth. The measurement of hair diameter showed that of 7603 hairs, 1241 were less than 40 microns in diameter, of which only 21 were more than 80 mm in length. Variation in the diameter of individual hair fibres was recorded. The number of hairs less than 40 microns diameter per cm2 of scalp was increased in both men and women with androgenic alopecia. It was concluded that the number of hairs greater than 40 microns in diameter per cm2 (meaningful density) reflected most closely the amount of hair usefully contributing to an individual's clinical appearance.

Presence and activity of LH-RH in the mid-term human fetus.

Immunoreactive LH-RH was present in all the hypothalamic and cortical extracts of mid-term human fetuses studied and in the cortical tissue removed from the two youngest fetuses. Gonadotrophin-releasing activity of hypothalamic and cortical extracts was demonstrated by the significant rises of circulating LH after infusion into oestrogen and progesterone-primed ovariectomized rats.

Thyrotoxicosis: relations between clinical state and biochemical changes during carbimazole treatment.

The relation between clinical and biochemical changes in thyrotoxicosis were studied in 12 patients with Graves's disease who were being treated with carbimazole. Clinical assessment (using the Crooks-Wayne index) was combined with the measurement of free thyroxine and triiodothyronine indices (FT4I and FT3I) and the assessment of two tissue markers of thyroid hormone action--sex-hormone-binding globulin (SHBG) levels and the thyrotrophin responses to TRH. In general the FT4I and FT3I fell rapidly once treatment was started, and returned to normal in one to four weeks, followed shortly by SHBG levels. The thyrotrophin response returned at this time in two patients, who still had borderline high levels of FT3I and SHBG. The clinical score fell more slowly and variably and was less closely related to any of the biochemical indices than these were to each other. During the early phase of treatment with antithyroid drug the clinical evaluation may be an unreliable indicator of persisting thyroid hormone excess, and when the patient seems clinically but not biochemically thyrotoxic the symptoms should be treated on their own merits with beta-blocking drugs and not with increased doses of antithyroid drugs.

Radioimmunoassay and chromatographic similarity of circulating endogenous gonadotropin releasing hormone and hypothalamic extracts in man.

A highly sensitive radioimmunoassay for the gonadotropin releasing hormone has been developed in order to study its physiological importance in man. In view of the expected low concentrations in peripheral blood, large volumes of human plasma were extracted by two different methods and characteristics of the radioimmunoassayable material compared with those of synthetic decapeptide and extracts of human hypothalami. The results indicate that radioimmunoassayable gonadotropin releasing hormone is present in some human plasmas but the plasma concentration are less than 2.5 pg/ml. Peripheral levels were more consistently measurable in women at midcycle and after the menopause. The hormone was undetectable in the plasma of normel men, human cerebrospinal fluid, and fetal cerebral tissue, but was present in fetal hypothalami.

Impairment of platelet function by growth-hormone release-inhibiting hormone.

Synthetic cyclic growth-hormone release-inhibiting hormone (G.H.-R.I.H.) impaired platelet aggregation in each of four healthy men given 6-hour infusions. The effects lasted over 24 hours in three of them. There was no consistent change in platelet-counts during the infusions, but 18 hours after the end of the infusions there was a slight but significant increase in platelet-count. There was no change in prothrombin-time, partial thromboplastin-time, fibrinogen titres, and fibrinogen-degradation products. Incubation of G.H.-R.I.H. with blood in vitro did not affect platelet aggregation. Similar impairment of platelet function has been reported by others in baboons given linear G.H.-R.I.H. Infusions in the four healthy men studied also produced abdominal pain, dizziness, and diarrhoea in three, as have been reported in patients similarly infused. Although other side-effects or impairment of platelet-counts or bleeding-tendencies have not been reported in patients infused for up to 72 hours, caution should be exercised when using G.H.-R.I.H. over extended periods until further data on its toxicity are available.

Bromocriptine treatment of acromegaly.

The effects of oral bromocriptine in acromegaly have been studied. A dose of 5 mg six-hourly suppressed circulating growth hormone (GH) levels in nine out of 11 patients treated for seven to 11 weeks. This was associated with considerable clinical improvement in all patients, with abolition of excessive sweating, reduction in soft-tissue thichening, loosening of rings, decrease in shoe size, improvement in facial features, and loosening of dentures. Metabolic changes included improvement in glucose tolerance and reduction in hydroxyproline excretion. Unlike the actions of growth hormone release inhibiting hormone the suppression of GH was not accompanied by a reduction in insulin or glucagon secretion, though prolactin levels were suppressed. Side effects other than mild constipation were not seen when the full dose regimen was reached by slowly increasing the dose from 2-5 mg once daily. Bromocriptine holds promise as a safe and orally effective medical treatment to augment surgical or radiotherapeutic measures directed at the pituitary tumour. Its efficacy during longterm administration remains to be established.

Gonadotrophin-releasing hormone therapy in hypogonadal males with hypothalamic or pituitary dysfunction.

Subcutaneous self-administration of synthetic gonadotrophin-releasing hormone 500 mug eight-hourly for up to one year by 12 male patients (five prepubertal) with clinical hypogonadism due to hypothalamic or pituitary disease resulted in the synthesis and continued release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). There was a rise in circulating androgen levels in all patients. Improvements in pubertal ratings were seen in some prepubertal patients. Potency returned in the adults and spermatogenesis was induced and maintained in the four patients who had received treatment for more than four months, total counts reaching between 7.8 and 432 x 10(6) spermatozoa. A fall in the FSH response to the releasing hormone occurred during spermatogenesis though LH was little affected. During the initial weeks of therapy FSH secretion usually occurred before that of LH though LH secretion was greater as treatment continued. FSH secretion also persisted for longer when treatment was stopped.

Long-term infusion of growth hormone release inhibiting hormone in acromegaly: effects on pituitary and pancreatic hormones.

Growth hormone release inhibiting hormone (GH-RIH) was infused at a rate of 1.3 mug/min for 28 hours into four patients with acromegaly, two of whom also had clinical diabetes mellitus. Growth hormone and glucagon were suppressed throughout the infusion though delayed secretion of insulin occurred in association with both meals and an oral glucose load. Glucose tolerance was improved in one diabetic patient who was taking chlorpropamide while the other required much less insulin than usual. Secretion of endogenous thyroid-stimulating hormone was lowered in one euthyroid patient on carbimazole. Luteinizing hormone, follicle-stimulating hormone, ACTH, and prolactin were not affected. Serum somatomedin levels were reduced in one patient. There was a rapid rebound of all the suppressed hormones when the infusions stopped. Longer-acting analogues of GH-RIH will be needed before long-term therapy of acromegaly or diabetes mellitus becomes possible, but such preparations should be available soon for clinical trial.