Gonadotropin release in infertile men following ketoconazole administration.

The pituitary gonadotropin releasing capacity of ketoconazole, (KC, p.o. 800 mg/day for 5 days), GnRH (i.v. 100 micrograms) and clomiphene, (CL, p.o. 100 mg/day for 7 days) was compared in 25 infertile male patients. It was found that KC resulted in a significant increase in serum LH (from 8.94 +/- 1.05 to 17.55 +/- 1.32 U/l), FSH (from 6.68 +/- 1.05 to 9.82 +/- 1.28 U/l), 17-OH-progesterone (from 4.51 +/- 0.34 to 11.35 +/- 0.68 nmol/l) and a decrease in serum testosterone (from 16.62 +/- 1.28 to 11.66 +/- 1.59 nmol/l) and dehydroepiandrosterone (from 6.56 +/- 0.39 to 4.82 +/- 0.37 mumol/l) levels. GnRH was effective in all patients, while CL failed to induce considerable amount of LH release (less than 2 U/l) in 7 patients and ketoconazole in 2 patients. It is important to note that KC was also effective in the CL resistant cases. Furthermore, it has been established that the amount of LH released by KC was midway between that of GnRH and CL. Almost 50 per cent of the patients failed to show a significant FSH release (less than 2 U/l), and in this respect, the three substances were similar. The KC test with its different mode of action can be recommended as a reliable diagnostic method in male patients.

New possibilities in the diabetic diet.

Recent changes in diabetic diet have been reviewed with special regard to the role of obesity, eating habits, carbohydrate content, and the ratio of simple and complex carbohydrates in meals, glycaemic index and fibre content of diet. The lack of standard conditions for comparing the results of different examinations as well as the need for the decisive results of long-term studies have been pointed out. The recommended carbohydrate content of diabetic diet is 60%, fat content 30-35%. The previous complete elimination of simple naturally occurring carbohydrates from the diet is not recommended anymore, these may be consumed in a wider field. The observance of glycaemic index and the use of high-fibre diet are of high importance--even if not primary--especially in type II diabetic patient. In general it is recommended to maintain/obtain an ideal body weight and to introduce a simple diet--planned not only for diabetics.

Neuroendocrinological effects of ketoconazole in rats.

The effect of ketoconazole on steroid synthesis was studied in intact (sham-operated) and castrated male and ovariectomized female rats. Rats were given 25 mg/kg ketoconazole twice a day im for 5 days. The influence of ketoconazole was also investigated on hormone release altered by GnRH, estradiol and haloperidol. The following hormones were measured: serum LH, PRL, testosterone, corticosterone, 17-OH-progesterone, estradiol, and dopamine content of the tubero-infundibular area. Ketoconazole treatment resulted in a significant decrease of testerone level (from 7.93 +/- 1.99 to 3.83 +/- 0.94 nmol/l), whereas LH, PRL, corticosterone and 17-OH-progesterone remained unchanged in the male rat. The effect of castration on LH level was reduced by ketoconazole in male (from 590 +/- 35 to 390 +/- 25 micrograms/l) and female rats (from 468 +/- 22 to 346 +/- 39 micrograms/l), but the GnRH-stimulated LH release in castrated and ovariectomized animals was unchanged. The suppressive action of estradiol on LH in ovariectomized rats was enhanced (from 160 +/- 41 to 64.6 +/- 12.9 micrograms/l), and its priming effect on PRL release was diminished by ketoconazole (from 598 +/- 81 to 281 +/- 66 micrograms/l). Ketoconazole failed to modify the tubero-infundibular dopamine content and haloperidol-induced PRL release. It can be assumed that in addition to its inhibitory role of steroid biosynthesis ketoconazole has an influence on central mechanisms underlying LH and PRL release.

Comparison of the serum hormone levels and histological findings in pituitary adenomas.

UNLABELLED: Thirty patients with pituitary adenomas were investigated: 20 with growth hormone producing acromegaly, 7 with prolactinoma and 3 with hormonal inactive adenoma. The correlation between the serum PRL, GH, TSH, levels, their response to 200 micrograms i.v. TRH, measured before the transsphenoidal adenomectomy and the size, the light microscopic (H.E. and Mallory staining), immunocytochemical and ultrastructural (performed in 17 cases) picture of the adenomas were evaluated. CONCLUSIONS: (a) there is no close correlation between the hormone granules detected in the pituitary adenoma cells - by light microscopic, immunocytochemical and electron microscopic methods - and the serum hormone levels, their response to TRH; (b) in hormonally active adenomas the immunocytochemical as well as the ultrastructural findings could be negative; (c) in one disease more hormones could give an immunopositive reaction; (d) in any types of investigated adenomas the TSH immunopositivity was always accompanied by PRL immunopositivity (6 cases); (e) the size and the clinical (serum) or cytological hormone activity of the adenomas were independent of one another; (f) the basal serum hormone level shows the hormonal activity of the pituitary adenoma best of all.

Differences in pituitary trophormone release between menstruating and non-menstruating acromegalic women.

The reaction of PRL, TSH, GH, LH and FSH has been studied after the administration of TRH and LHRH to 15 acromegalic women of fertile age. According to the presence or absence of menstruation the patients were divided into 2 groups: 8 patients menstruated regularly, 7 had secondary amenorrhoea. The results of the two groups were compare with each other and to findings in a group of healthy controls (9 women). It was found that in secondary amenorrhoea basal PRL values significantly exceeded those registered in the menstruating group and in the controls. PRL reaction was similar in the controls and the secondary amenorrhoea group, but the menstruating patients showed lower values than those of the control group. TSH release did not differ in the three groups. In secondary amenorrhoea paradoxical GH-reaction after TRH-LHRH in the 15th minute significantly exceeded the value of the menstruating group and its whole course pointed to a more intensive reaction. In secondary amenorrhoea both basal LH and FSH secretion as well as LH and FSH release fell far below the values of the menstruating group. The onset of amenorrhoea was not related to the duration of acromegaly. Disturbances of gonadotrophin secretion may be induced by disorders of regulatory mechanisms as well as by the damaging effect of the adenoma on normal pituitary tissue.

Liquid crystal thermography of the thyroid.

The results of 102 thyroid liquid crystal thermography (LCT) examinations are discussed. Clinical and laboratory examination, scintigraphy, ultrasonography and LCT were performed in all of the cases. LCT is not suitable for obtaining morphological data and not accurate enough in evaluating thyroid function, but it is a good additional study. It is inexpensive, not hazardous and fast, and can be the first examination in an endocrine outpatient clinic as well as in the follow up of patients with thyroid disease.

Effects of a 72-hour prostacyclin infusion on the hormone levels in patients with obliterative arterial disease.

Effects of a 72-h prostacyclin (PGI2) infusion (5 ng/kg/min) on hormone levels were studied in 11 patients (5 males, 6 females) suffering from obliterative arterial disease of the lower extremities. ACTH, cortisol, TSH, prolactin (Prl), GH, LH, FSH, T3, T4, calcitonin, parathyroid hormone (PTH), insulin, plasma renin activity (PRA), aldosterone and testosterone levels were measured at -15, 0, 30, 120, 240 min and 24, 48, 72 and 96 h after the infusion. During the first 240 min Prl and GH levels showed an increase that was thought to be either an effect of release of hormones or a consequence of stress. At the same time the thyroid hormones, T3, T4 and calcitonin decreased, presumably owing to an alteration in the blood flow to the thyroid gland. All these hormone levels returned to normal at 24 h in spite of the infusion continuing. PRA increased only during the second half of the infusion. No changes were found in the levels of ACTH, cortisol, TSH, LH, FSH, PTH, insulin, aldosterone and testosterone during the infusion. Five diabetics showed the same hormonal changes as the non-diabetics and their blood sugar levels remained unaffected during and after the procedure.

Growth hormone producing pituitary adenoma and meningioma.

A 59 years old woman is presented with acromegaly caused by an adenoma of the hypophysis, mixed cell-type and with a meningioma fibromatosum localized centroparietally. Both tumours were operated successfully, first the meningioma was removed. The hormone levels did not change after the operation of the meningioma, but normalized after the removal of the hypophysis adenoma. The simultaneously occurrence--without previous irradiation--of such tumours is very rare.

Effect of a somatostatin analogue on trophic hormone levels in acromegalic patients with elevated hGH after adenomectomy and treatment with bromocriptine.

Five female acromegalic patients who had undergone surgical adenomectomy, but still had elevated hGH serum levels, were treated with bromocriptine, 5-15 mg daily, for at least 4 months without a satisfactory response. In an attempt to lower serum hGH levels, p-NH2-Phe4-D-Trp8-somatostatin was administered, 100 micrograms as an i.v. bolus, followed by infusion of 250 micrograms over a 4 hour period. The analogue decreased hGH levels by about 50% in 3 out of 5 patients, both during bromocriptine treatment and also in its absence. Of the remaining two patients, one showed a decrease in hGH levels in response to the analogue only during bromocriptine treatment and the other only without it. Saline infusion after bromocriptine administration did not induce a decrease in hGH levels in three of these patients. Somatostatin analogue caused a fall in serum insulin levels in all but one patient, who had diabetes mellitus and in whom serum insulin was undetectable. Both hGH and insulin levels showed a significant rebound after infusion of the analogue, but returned to basal levels within 24 hours. Prolactin did not change during the analogue infusion in 4 patients with normal PRL levels. However, in one patient in whom prolactin and hGH levels were elevated during bromocriptine treatment, the infusion of somatostatin analogue decreased both hormones. The analogue induced no changes in serum TSH, FSH and LH levels of any of the patients.

Hypoadrenia following adrenal venography in Cushing's disease.

Three patients with Cushing's disease are reported. In two patients the hyperfunction of the adrenal glands ceased following selective adrenal venography, moreover hypoadrenia has developed. In the third case necrosis following venography was proved by surgery and confirmed by histology. Regarding the therapeutic possibilities of Cushing's disease the use of this diagnostic procedure is taken into consideration but not recommended.

Effect of thyrotropin-releasing hormone and gonadotropin-releasing hormone on serum TSH, PRL, hGH, FSH and LH in primary testicular failure and in hypogonadotrophic hypogonadism.

Infertile males with primary testicular failure, 6 with normal (Group I) and 7 with elevated gonadotropin levels (Group II), 9 patients with Klinefelter's syndrome (Group III) and 5 patients with hypogonadotrophic hypogonadism (Group IV) were investigated. Their serum TSH, PRL, hGH, FSH and LH responses to a single bolus of 200 micrograms TRH and 100 micrograms GnRH were measured and compared to the corresponding values obtained in 8 fertile healthy males of the same age group. The testosterone levels differed from the control only in the last two groups. Neither the basal TSH level nor the delta TSH differed between the groups. The latter was significant in all groups. The basal PRL level was similar in each group except in Group II. where the level was low. After TRH-GnRH treatment the PRL level increased significantly in each group but this increase was less in patients with hypogonadotrophic hypogonadism (9.94 +/- 2.6 nmol/l) when compared to the patients with primary testicular failure (Groups I, II, III, together, n = 22 17.10 +/- 2.12 nmol/l P less than 0.05). The basal levels of hGH and delta GH did not differ significantly between the groups. Both FSH and LH showed an exaggerated and protracted increase in patients with primary testicular failure with elevated basal gonadotropin level after TRH-GnRH, while in hypogonadotrophic hypogonadism the response was slight. Neither the serum testosterone nor the serum FSH or LH level influenced the response of TSH and hGH to the TRH-GnRH test.

Liquid crystal thermography of the testicles in the diagnosis of infertility.

The use of liquid crystal thermography (LCT) of the testicles in diagnosis of infertility was investigated. Varicocele, the most common cause of male infertility, is easily detectable by LCT. The technique may be used as a control after surgical treatment. In the majority of patients with oligo-azoospermia, LCT corresponded to physical examination of the testicles. In patients with oligo-azoospermia and both testicles normal to palpation, LCT is useful method for determining the colder testicle for biopsy purposes.

[Simultaneous occurrence of pituitary adenoma and thyrogenic hyperthyroidism]. / Gleichzeitiges Auftreten eines Adenoms der Hypophyse und einer thyreogenen Hyperthyreose.

Subtotal tumour removal had been performed in a 34-year-old female patient for an extensive intra- and suprasellar expansive process. The considerably increased prolactin level did not decrease postoperatively, but normalised only after a three months bromocriptine treatment. The primary hyperthyroidism has been recovering after administering methimazolum. In a second case was reported on a 65-year-old female patient, suffering from rachitic dwarfism, stenosis of the aortic valve and tumour of the hypophysis, causing acromegaly, whose diabetes mellitus of contrainsular type could have been hardly balanced with insulin of a 128-unit-dose daily, and whose hyperthyroidism was due to an autonomous adenoma of the thyroid gland, first I-131 treatment was administered and she got into an euthyroid state. Six weeks following the removal of the acidophilic adenoma of the hypophysis administration of insulin could have been ceased, and the results of her growth hormone became normal. The clinical picture partly corresponds with Troell-Junet's syndrome.

The possible reason for serum 3,3'5'-(reverse) triiodothyronine increase in old people.

Healthy subjects aged 70-90 and 20-40 years were investigated for the level of reverse triiodothyronine (rT3). The mean level in 57 old subjects was higher and the triiodothyronine (T3) level lower than in 30 young persons. No negative correlation was observed. A serum T3 elevation caused by liothyronine administration (5-15 micrograms/day for two weeks) was not followed by a change of the mean rT3 level in 12 old subjects. After a single intramuscular thyrotropin (TSH) injection, the rT3 elevation lasted 24h longer in 19 old persons than in the 9 control ones, though the early rT3 response was similar in both groups. Propranolol administration (40 mg t.i.d. for a week) caused a similar rT3 elevation in old persons (n = 18) as in 12 young ones. From the indirect data it is concluded that the serum rT3 elevation in old age is a result of faster peripheral generation and not of increased production in the thyroid gland. The data do not indicate any change of rT3 metabolism. T4-T3 and T4-rT3 conversion are provoked by different enzymes. The elevation of rT3 might be a cause of the observed decrease in peripheral T3 generation in old subjects, acting by an inhibition of the T4-T3 conversion.

Oddi's sphincter spasm in hypocalcaemia of dogs.

1. Decreases of serum calcium concentration in dogs lead to increased basal tone of Oddi's sphincter in the employed experimental model. 2. This effect is independent of the agent used for decreasing the serum calcium level. 3. Spasmolysis was observed immediately after the injection of CaCl2. CaCl2 alone, however, had no effect in "normocalcaemic" animals. 4. Local decrease of calcium level plays no significant role in the sphincter spasm. It is suggested that the spasm is elicited by increased smooth muscle excitability as a consequence of the hypocalcaemic state prevailing in the body.