Hypothalamo-hypophyseo-gonadal axis in individuals with chronic renal insufficiency subjected to hemodialysis

The role of pituitary and sexual hormones in 21 patients with chronic renal failure (CRF) and related impotence and loss of libido who were being treated by hemodialysis and in 15 normal male controls has been studied. In both groups the serum levels of FSH, LH and TSH, PRL before and after injection of both LHRH and TRH were measured as well as the basal levels of Testosterone (T) and Estradiol (E2). The results show similar values for testosterone in both groups and statistically significant higher basal values for FSH, LH, TSH and PRL and lower basal values for E2 in CRF patients.     

Effects of chronic anticonvulsant monotherapy on endocrine system in prepubertal children with convulsive disorders. Preliminary data

Effects of phenobarbital (PB), carbamazepine (CBZ) and sodium valproate (VPA) monotherapy on endocrine functions were investigated in 7 clinically prepubertal children aged 5-10 8/12 years. The following meaning results were observed: normal PRL release, low basal T4 levels in PB-, CBZ-treated children and normal T4 basal level in the VPA-treated child; normal T3, rT3, TBG and TSH basal values and normal TSH release in all treated children, normal FSH release in PB-, CBZ- and VPA-treated females, high LH levels before and after LHRH injection in CBZ- and PB-treated females; normal levels in the VPA-treated one, normal basal FSH levels and increased releases in PB- and CBZ-treated males, high LH levels before and after LHRH injection in PB- and CBZ-treated males, normal basal and peak levels of GH.     

Effect of non aromatizable androgens on LHRH and TRH responses in primary testicular failure

We have assessed the gonadotropin, TSH and PRL responses to the non aromatizable androgens, mesterolone and fluoxymestrone, in 27 patients with primary testicular failure. All patients were given a bolus of LHRH (100 micrograms) and TRH (200 micrograms) at zero time. Nine subjects received a further bolus of TRH at 30 mins. The latter were then given mesterolone 150 mg daily for 6 weeks. The remaining subjects received fluoxymesterone 5 mg daily for 4 weeks and 10 mg daily for 2 weeks. On the last day of the androgen administration, the subjects were re-challenged with LHRH and TRH according to the identical protocol. When compared to controls, the patients had normal circulating levels of testosterone, estradiol, PRL and thyroid hormones. However, basal LH, FSH and TSH levels, as well as gonadotropin responses to LHRH and TSH and PRL responses to TRH, were increased. Mesterolone administration produced no changes in steroids, thyroid hormones, gonadotropins nor PRL. There was, however, a reduction in the integrated and incremental TSH secretion after TRH. Fluoxymesterone administration was accompanied by a reduction in thyroid binding globulin (with associated decreases in T3 and increases in T3 resin uptake). The free T4 index was unaltered, which implies that thyroid function was unchanged. In addition, during fluoxymesterone administration, there was a reduction in testosterone, gonadotropins and LH response to LHRH. Basal TSH did not vary, but there was a reduction in the peak and integrated TSH response to TRH. PRL levels were unaltered during fluoxymesterone treatment.(ABSTRACT TRUNCATED AT 250 WORDS)     

Resolution of possible paradoxical responses of gonadotropins to thyrotropin-releasing hormone with bromocriptine therapy in a patient with follicle-stimulating hormone-secreting pituitary adenoma.

We report the effectiveness of bromocriptine therapy in resolving the abnormal responses of plasma FSH and LH to TRH in a 70-year-old male with FSH-secreting pituitary macroadenoma who had unsuccessful transsphenoidal pituitary surgery. In the pre-treatment and post-operative periods, respectively, basal plasma levels of FSH were increased to 88.7 and 65.6 mIU/ml (normal range; 8.5-32.4) but those of plasma LH were normal being 7.0 and 4.1 mIU/ml; (normal range; 4.1 to 14.0). The responses of plasma FSH and LH to LHRH were exaggerated and their paradoxical responses to TRH were highly suggested. During the bromocriptine therapy, the basal level of plasma FSH was normalized and that of plasma LH remained normal. The magnitude of FSH and LH responses to LHRH decreased and their paradoxical responses to TRH were completely resolved.     

Effect of bombesin on basal and stimulated secretion of some pituitary hormones in humans

The effect of bombesin (5 ng/kg/min X 2.5 h) on basal pituitary secretion as well as on the response to thyrotropin releasing hormone (TRH; 200 micrograms) plus luteinizing hormone releasing hormone (LHRH; 100 micrograms) was studied in healthy male volunteers. The peptide did not change the basal level of growth hormone (GH), prolactin, thyroid-stimulating hormone (TSH), luteinizing hormone (LH) and follicle-stimulating hormone (FSH). On the contrary, the pituitary response to releasing hormones was modified by bombesin administration. When compared with control (saline) values, prolactin and TSH levels after TRH were lower during bombesin infusion, whereas LH and FSH levels after LHRH were higher. Thus bombesin affects in man, as in experimental animals, the secretion of some pituitary hormones.     

The hypothalamic-pituitary axis in diabetes mellitus

The hormonal response to LHRH and TRH was evaluated in three groups of male diaetics. Five patients were receiving therapy with the hypoglycemic agent glibenclamide, five were on NPH insulin and five were on dietary therapy alone. When compared to controls, the latter two groups had intact gonadotropin responses to LHRH. Despite normal basal gonadotropin levels, however, the group receiving glibenclamide therapy showed significantly exaggerated LH and FSH responses to LHRH. Both basal PRL and TSH levels, as well as the responses to TRH were normal in all three groups. These results indicate that LH, FSH, TSH and PRL secretion is intact in uncomplicated diabetes mellitus. The exaggerated LH and FSH responses to LHRH in the glibenclamide treated subjects are probably related to primary gonadal involvement; alternatively, there may be augmented pituitary gonadotropin secretion in this group.     

Cyclosporine A inhibits the secretion of certain anterior pituitary hormones in patients with nephrotic syndrome.

To clarify the effects of cyclosporine A (CsA) on the secretion of serum thyrotropin (TSH), prolactin (PRL), luteinizing hormone (LH) and follicular stimulating hormone (FSH), we performed TRH and LH-RH testing in 4 patients with the nephrotic syndrome before and after the administration of CsA, 6 mg/kg/day for 4 to 12 weeks. Prior to CsA all patients responded normally to TRH with respect to TSH and PRL secretion. Two patients showed normal response of LH and FSH to LH-RH stimulation while the response in 2 other patients, who were both menopausal, was exaggerated. By the third or fourth week of CsA administration the basal and peak TSH and PRL values declined significantly in all patients in response to TRH stimulation while those of LH and FSH showed only a modest decrease in response to LH-RH stimulation. Two to 4 weeks after the cessation of CsA the response of TSH, PRL and FSH returned to the pretreatment level. These observations suggest that: 1) CsA exerts an inhibitory effect on the secretion of at least TSH and PRL in humans, and 2) the effect of CsA on the pituitary may be partially reversible after the cessation of the therapy.     

Effect of triiodothyronine administration on the plasma TSH and prolactin responses to TRH in patients with hypothalamic-pituitary insufficiency.

A study was carried out in 10 patients with multiple pituitary hormone deficiencies to determine the response of thyroid-stimulating hormone (TSH) and prolactin (PRL) to thyrotropin-releasing hormone (TRH) and their suppressibility by treatment with triiodothyronine (T3) given at a dose of 60 microgram/day for 1 week. In 3 patients the basal tsh values were normal and in 7 patients, 2 of whom had not received regular thyroid replacement therapy, they were elevated. The response of TSH to TRH was normal in 6 patients and exaggerated in 4 (of these, 1 patient had not received previous substitution therapy and 2 had received only irregular treatment). The basal and stimulated levels of TSH were markedly suppressed by the treatment with T3. The basal PRL levels were normal in 7 and slightly elevated in 3 patients. The response of PRL to TRH stimulation was exaggerated in 2, normal in 6 and absent in 2 patients. The basal PRL levels were not suppressible by T3 treatment but in 4 patients this treatment reduced the PRL response to TRH stimulation. From these findings the following conclusions are drawn: (1) T3 suppresses TSH at the pituitary level, and (2) the hyperreactivity of TSH to TRH and the low set point of suppressibility are probably due to a lack of TRH in the type of patients studied.     

Pharmacodynamic tests of the stimulation of hypophyseal function: simplification of the procedure without alteration of their diagnostic value

The aim of this study was to examine if it was possible to simplify the procedure of some stimulation tests of pituitary function. This study was performed on 300 stimulation tests of TSH by TRH, PRL by TRH, LH by LHRH and FSH by LHRH, respectively. Simplified procedures may be proposed without altering the diagnostic value of the tests: assay of TSH and PRL 0 and 30 minutes after TRH injection and of LH and FSH 0, 30 and 60 minutes after LHRH injection.     

Prevalence of endocrine dysfunction in HIV-infected men

OBJECTIVE: Endocrine dysfunction is a common problem in patients with human immunodeficiency virus infection (HIV). We therefore evaluated the endocrine function in 31 male homosexual HIV-1-infected men: mean age 37 +/- 7.2 years (range 24-52). METHODS AND MATERIALS: Blood was obtained for baseline T3, T4, TSH, LH, FSH, prolactin, testosterone, ACTH and cortisol values. Endocrine function tests were performed as TRH, CRH, ACTH, LH-RH and HCG tests. RESULTS: Thyroid function: There was a temporarily increased TSH in 3 of 17 patients but normal levels for T3, T4 and fT4 (without thyroid antibodies). One patient showed signs of latent hyperthyroidism (no response in TRH test). Adrenocortical function: Two patients had adrenal insufficiency. They showed a normal baseline cortisol level, an elevated ACTH level and no increase in cortisol levels after stimulation with CRH. All other patients revealed normal responses on the CRH/ACTH tests. Gonadal function: 9 patients had elevated FSH levels (tubular insufficiency), 4 patients additionally had increased LH levels (hypergonadotropic hypogonadism). 5 patients showed signs of tertiary hypogonadism (low LH and testosterone, increase of LH after stimulation with LH-RH). CONCLUSION: In disorders of thyroid and adrenocortical function of primary or tertiary origin, a substitution of hormones should be taken into consideration.     

Prospective study on the influence of radiochemotherapy on pituitary function in children with acute leukaemia and NHL.

To assess effects of chemo- and radiotherapy on the endocrine system 31 children with acute leukaemia and NHL (3 AML, 24 ALL, 4 NHL) were investigated. Children were treated according to modified BFM protocols. 25 patients were before, 5 during and one after puberty (2 to 16 y.). Before treatment, during induction therapy, during cranial irradiation, 4-6 weeks later and during maintenance therapy the following hormone values were estimated: TSH and prolactin basal and 30 min. after TRH (5 micrograms/kg i.v.), LH and FSH basal. Final investigations included total T4 and T3. In conclusion, chemo- und radiotherapy lead to transient elevations of TSH and prolactin in a few patients, but without proof for permanent disorders. Due to the fact all 3 patients with hyperprolactinaemia showed high prolactin levels (700 to 770 mU/l) already before treatment it is unlikely therapy was the main cause of these observed alterations. Although basal LH and FSH values were in normal ranges for age the increasing values after cranial irradiation in prepubertal children may reflect a possible initiation of early maturation, reported by others. Furthermore a retrospective growth study was performed in children treated with 2 different protocols. Protocol LSA2L2 used in the past before 1981 resulted in a permanent reduction of the height. In contrast, the mean SDS for height in children treated with protocol VII declined only during the intensive period of treatment. A catch-up growth occured already during maintenance therapy. Prophylactic cranial irradiation with 18 Gy in our patients under protocol LSA2L2 did not affect growth during the first 5 years after diagnosis.     

Changes in the hypothalamic-pituitary-thyroid axis during acute starvation in non-obese patients

We investigated changes in the hypothalamic-pituitary-thyroid axis before, during, and after fasting in twenty-one non-obese euthyroid patients with psychosomatic diseases. Blood samples for free T3 (FT3), T3, free T4 (FT4), T4, reverse T3 (rT3), and TSH were obtained from all patients before and on the 5th day of fasting, and in 11 of the same individuals on the 5th day of refeeding. Serum TSH and T3 responses to TRH were also evaluated in 10 patients before and on the 5th day of fasting. During the fast, FT3, T3 and TSH levels decreased significantly and rT3 levels increased significantly whereas FT4 and T4 levels remained within the normal range. Maximal delta TSH, peak TSH levels, max delta T3, peak T3 levels, and net secretory responses to TRH decreased significantly. Peak TSH levels and max delta TSH to TRH correlated well with basal levels of TSH. A statistically significant negative correlation between basal levels of FT4 and TSH was observed. After refeeding, there was a significant increase only in TSH which returned to prefasting values. These results demonstrated that in a state of "low T3" during acute starvation a reduction in serum T3 might depend partly on TSH-mediated thyroidal secretion.     

Anterior pituitary function in Cushing's syndrome: study of 36 patients.

We studied the anterior pituitary function in 36 patients (25 females and 11 males, mean age: 35 years) with untreated Cushing's syndrome by simultaneous triple stimulus with insulin, TRH and LHRH. Thirty-one patients (86%) had Cushing's disease and five (14%) had an adrenal adenoma. We observed a lack of response of GH to hypoglycemia in 88%, TSH to TRH in 91%, LH to LHRH in 30%, FSH to LHRH in 12% and PRL to TRH in 6% of the patients. Low-to-normal total thyroxine (T4) values were obtained in 37%, with low triiodothyronine levels in 87%. The free-T4 index was normal in all patients. Total testosterone was low in only one adult man, while estradiol and progesterone were low in 45% and 15% of premenopausal women, respectively. We observed no differences in either axis among patients with Cushing's syndrome of different etiologies. Nor was there any statistical difference between the frequency of alteration of each axis and the levels of urinary free cortisol or the duration of the disease. We conclude that hypercortisolism is responsible for the abnormalities in anterior pituitary function in Cushing's syndrome.     

Influence of D-thyroxine on plasma thyroid hormone levels and TSH secretion.

Triiodothyronine (T3), thyroxine (T4), basal TSH and TSH after stimulation with TRH were determined in healthy subjects and patients treated with D-thyroxine (DT4). After a dosage of 6 mg DT4 the D/L T4 plasma concentration rose about 4-fold 4 hours after application and was only moderately elevated 14 hours later. To achieve constantly elevated T4 levels 3 mg DT4 were applied in the further experiment every 12 hours. The D/L T4 plasma concentration rose 2.5-4-fold and there was a small but significant increase of the D/L T3 plasma concentration. 74 hours after onset of treatment basal TSH was below detectable limits and the increase of TSH 30 min after injection of 200 mug TRH (TRH test) was only about 15% compared to zero time. The time course of TSH suppression was investigated after treatment with DT4 and LT4 (single dosage of 3 mg). TRH-tests were performed before, 10, 26, 50 and 74 hours after the first dosage of D or LT4. There was no difference in the time course of basal TSH and TSH stimulated by TRH. In 10 patients on DT4 long-term therapy, basal and stimulated TSH were found to be below the detectable limits of 0.4 mug/ml. Our results show that (1) plasma half-life of DT4 is less than 1 day, (2) TSH suppression after D and LT4 treatment is very similar, and (3) in patients on long-term DT4 treatment, TSH plasma concentration is below detectable limits even after stimulation with TRH.     

Dissociation of thyrotropin and prolactin responsiveness to thyrotropin releasing hormone stimulation in L-dopa treated parkinsonian patients

The hPRL, hTSH and T3 response to thyrotropin releasing hormone (TRH) stimulation (200 microgram i.v.) were studied in 8 parkinsonian patients under chronic L-dopa-carbidopa therapy. In 6 out of the 8 patients studied, treatment was stopped for a period of 2 weeks and the TRH stimulation test was repeated under similar experimental conditions. In the L-dopa-carbidopa treated patients basal hTSH levels and the hTSH response to TRH were significantly suppressed. By contrast, in the 6 patients 2 weeks after cessation of treatment, although basal hTSH levels were still suppressed, a normal hTSH response to TRH was observed. Neither the basal T3 and T4 concentrations, nor the T3 response to TRH were affected by the L-dopa-carbidopa treatment. In addition, basal hPRL levels as well as the hPRL: response to TRH were within the normal range in the two groups of patients studied. Our study provides further support for a dopaminergic inhibitory action on the hypothalamo-hypophyseal-thyroidal axis (HHTA). The inhibition of basal hTSH secretion and th hTSH response to TRH by L-dopa, suggest that the blocking action of dopamine is exerted at the hypothalamic as well as at the pituitary level. In our hands, chronic administration of L-dopa did not affect either tonic hPRL secretion of the hPRL response to TRH. The dissociation or response to TRH under the same inhibitory action of dopaminergic stimulation can be interpreted as demonstrating a greater sensitivity of the pituitary thyrotrophs, than the prolactin secreting cells, to the blocking effect of dopamine.     

Effects of continuous LHRH infusion on plasma levels of LH and FSH in males, before and after oestrogen or anti-oestrogen treatment

In order to study the role of oestrogens on gonadotrophin release in the human male, LHRH was administered as an infusion at a constant rate of 0.5 micrograms/minute for 4 hours to 7 normogonadotrophic oligozoospermic men, 6 eugonadal male-to-female transsexuals and 9 eugonadal male volunteers. In agreement with in vitro data a biphasic release pattern of both LH and FSH was observed in eugonadal transsexuals as well as in normogonadotrophic oligozoospermic men. In the latter the release of LH was greater than in eugonadal transsexual males and volunteers, which points to a different functioning of the hypothalamic-pituitary unit in normogonadotrophic oligozoospermic men. On the other hand the FSH response to LHRH stimulation was normal in these men. Three months' treatment with the oestrogen-receptor antagonist tamoxifen (TAM) (10 mg twice daily) in the normogonadotrophic oligozoospermic men stimulated basal LH, FSH and testosterone (T) levels. The fact that gonadotrophin levels rose in spite of increased T levels, suggests a role of endogenous oestrogens in the negative feedback regulation of gonadotrophin release in these men. Upon TAM treatment the first phase, the plateau and the second phase of LH release were augmented, whereas only the plateau and the second phase of FSH release were increased. Six weeks' administration of the oestrogen ethinyloestradiol (EE) (10 micrograms three times a day) in the eugonadal transsexual males suppressed basal T and oestradiol (E2) levels without affecting basal gonadotrophin levels significantly. In EE-treated males the first phase of LH release tended to be lower, whereas the plateau of LH had decreased significantly. The second phase of LH was unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)     

The pituitary-thyroid axis in patients with pituitary disorders

The pituitary-thyroid axis of 12 patients, exposed to transsphenoidal pituitary microsurgery because of nonfunctioning adenomas (6), prolactinomas (3) and craniopharyngioma (1), or to major pituitary injury (1 apoplexy, 1 accidental injury), was controlled more than 6 months following the incidents. The patients did not receive thyroid replacement therapy and were evaluated by measurement of the serum concentration of thyroxine (T4), 3,5,3'-triiodothyronine (T3), 3,3',5'-triiodothyronine (rT3), T3-resin uptake test and thyrotropin (TSH, IRMA method) before and after 200 micrograms thyrotropin releasing hormone (TRH) iv. The examination also included measurement of prolactin (PRL) and cortisol (C) in serum. Apart from 1 patient with pituitary apoplexy all had normal basal TSH levels and 9 showed a significant TSH response to TRH. Compared to 40 normal control subjects the 12 patients had significantly decreased levels of T4, T3 and rT3 (expressed in free indices), while the TSH levels showed no change. Five of the patients, studied before and following surgery, had all decreased and subnormal FT4I (free T4 index) after surgery, but unchanged FT3I and TSH. The levels of FT4I were positively correlated to both those of FT3I and FrT3I, but not to TSH. The TSH and thyroid hormone values showed no relationship to the levels of PRL or C of the patients exposed to surgery. It is concluded that the risk of hypothyroidism in patients exposed to pituitary microsurgery is not appearing from the TSH response to TRH, but from the thyroid hormone levels.     

A possible role for cyclic GMP in mediating the effect of luteinizing hormone releasing hormone on gonadotropin release in dispersed pituitary cells of the female rat.

In continuing studies on cyclic nucleotide involvement in the regulation of gonadotropin release, we have measured the cyclic nucleotide content and rate of LH and FSH release during stimulation by LHRH of dispersed overnight cultured cells from the pituitaries of adult female rats. The minimal effective concentration of LHRH was 0.1 nM and half maximal stimulation of gonadotropin release was observed in the presence of 1.0 nM LHRH. Significant release of both LH and FSH was detectable after only 10 min in the presence of 5 nM LHRH. The presence of fetal calf serum (FCS) in the overnight culture medium increased basal cGMP levels significantly, whereas horse serum (HS) had no effect, therefore all experiments were conducted on cells cultured in the presence of HS. Treatment of the cultured cells with the phosphodiesterase inhibitors theophylline (TH) or isobutyl-methyl-xanthine (MIX) revealed a preferential stimulatory effect of TH on basal cAMP levels and of MIX on cGMP levels. Throughout these experiments, LHRH had no effect on cAMP levels. In the presence of MIX, concentrations of the releasing hormone as low as 1 nM induced a significant rise in the level of cGMP whereas in its absence, cGMP levels appeared to be unchanged by LHRH. The increase was detectable after 10 min of incubation. MIX alone slightly increased LH and FSH release and significantly potentiated the response of the cells to increasing doses of LHRH up to, but not beyond, 10 nM. The data support the possibility that cGMP may be involved in the mechanism of action of LHRH.     

The time interval effect on two consecutive LHRH-TRH tests on adult female baboons

To Clarify the relationship between the time interval and pituitary Luteinizing hormone (LH), Follicular stimulation hormone (FSH) and prolactin (PRL) secretion function under LHRH-TRH stimulation, 4 mature female baboons were used. Two consecutive LHRH (100 micrograms)-TRH (250 micrograms) stimulations with a 60 min interval between them was carried out in the early follicular phase, late follicular phase and mid luteal phase in the same baboon in the first menstrual cycle, then carried out with a 120 min interval between tests in the third menstrual cycle. The LH, FSH and PRL were measured by specific radioimmunoassay. The PRL maximum response to the first bolus of TRH was higher than maximum response to the second bolus of TRH. The PRL maximum response to the second TRH at a 120 min interval was higher than the maximum response to the second TRH at a 60 min interval. It seems that the TRH had the dominant effect on PRL releasing but not on PRL Priming. The maximum LH response to the second bolus of LHRH was higher than the maximum response to the first bolus of LHRH. The LH maximum response to the second bolus of LHRH at a 60 min interval was greater than the maximum response at a 120 min interval in the follicular phase but it was the reverse in the luteal phase. The FSH response to the second LHRH was different from the LH response.(ABSTRACT TRUNCATED AT 250 WORDS)     

Relationship of iodide-induced increase in TSH response to TRH to changes in serum thyroid hormones.

Large doses of iodide (500 mg three times a day) administered to normal men for 10--12 days caused a rise in basal serum TSH and a concomitant rise in the peak TSH response to TRH. The basal and peak levels of TSH were highly correlated (p less than 0.001). However, the iodide-induced rise in the peak TSH after TRH was poorly correlated with concomitant changes in serum thyroid hormones. Serum T3 wa not lower after iodide and, while serum T4 was somewhat lower, the fall in serum T4 was unexpectedly inversely rather than directly correlated with the rise in the peak TSH response to TRH. Thus, increased TSH secretion after iodide need not always be directly correlated with decreased concentrations of circulating thyroid hormones even when large doses of iodide are used. Clinically, a patient taking iodide may have an increased TSH response in a TRH stimulation test even though there is little or no change in the serum level of T3 or T4.