Exaggerated LH Response Research Articles

Successful pregnancy after the treatment of primary amenorrhea in a patient with non‐classical congenital adrenal hyperplasia

We describe a case of non-classical congenital adrenal hyperplasia (NCCAH) due to 21-hydroxylase deficiency in a 30-year-old Japanese woman who achieved pregnancy after treatment of primary amenorrhea. Hirsutism and clitoromegaly were present. Ultrasound examination showed polycystic appearance of the ovary. Luteinizing hormone-releasing hormone (LH-RH) test resulted in exaggerated LH response, showing a polycystic ovary syndrome (PCOS) pattern. The diagnosis was based on the elevated intial levels of 17-hydroxyprogesterone (55 ng/mL) and dihydroepiandosterone (7780 ng/mL). The first withdrawal bleeding occurred within 6 weeks after treatment with hydrocortisone (20 mg/day) combined with conjugated estrogens (1.25 mg/day) and medroxyprogesterone acetate (10 mg/day), which were continued for five courses. The bleeding remained cyclic every 28 days with maintenance doses of hydrocortisone. Subsequently, ovulation was induced using clomiphene citrate (100 mg/day). Pregnancy was achieved at the second attempt of ovulation induction and was within 10 months after initial presentation. Continuing hydrocortisone, the patient delivered a healthy baby at term.

A nonspecific disturbance of the gonadostat in women with transsexualism and isolated hypergonadotropism in the male-to-female disturbance of gender identity.

Principal parameters of gonadostat function were determined in 15 female-to-male (F-M) and 7 male-to-female (M-F) transsexual patients (T), all homosexuals. The data were compared with normal heterosexual controls of the respective sex. Anamnesis revealed prolongation of the menstrual cycles in F-M patients, mainly in those taking previously medication with depot-testosterone. However, also in patients with no previous medication the basal body temperature chart revealed anovulatory cycles (all 4 examined patients). In 8 of 9 patients (82.2%) with no previous medication an elevation of serum testosterone was found (63-600 ng/dl). No disturbances in gonadal functions were found in M-F group (semen analysis), serum testosterone was normal (328-710 ng/dl) except 1 case with reduced testosterone level (200 ng/ml). Both women and men with transsexualism revealed significantly higher mean basal serum concentration of LH in comparisons to controls (F-M: 23.14 +/- 16.16 vs 7.56 +/- 4.23; M-F 15.30 +/- 6.49 vs 5.75 +/- 3.66). No changes in basal serum FSH concentration were present. GnRH test (100 micrograms i.v.) revealed decreased evocability of LH in woman with T and exaggerated LH response in men with T. FSH hyperresponse to GnRH was nonsignificant in F-M and significant in M-F T. It is concluded that F-M transsexualism is associated with nonspecific disturbances of gonadostat since hypergonadotropism coexists with the signs of impaired gonadal function. In M-F T and isolated hypergonadotropism coexisted with specific, increased sensitivity of the pituitary to GnRH.

POLYCYSTIC OVARY SYNDROME

The cardinal clinical features of PCOS are hirsutism and menstrual irregularity from anovulation. Obesity occurs in approximately 50% of hyperandrogenic anovulatory women, some of whom also have non-insulin-dependent diabetes mellitus. Underlying these clinical findings are several biochemical abnormalities, including LH hypersecretion, hyperandrogenism, acyclic estrogen production, decreased SHBG capacity, and hyperinsulinemia, all of which contribute to increased ovarian production of androgens, particularly T. A fundamental mechanism of ovarian hyperandrogenism in PCOS is LH hypersecretion. Whether the central nervous system is a possible locus for initiating LH hypersecretion remains unclear, because exaggerated LH secretion is temporarily reversed by induced ovulatory cycles or physiologic luteal concentrations of progesterone. On the other hand, desynchronization of pulsatile LH secretion from sleep in girls with PCOS and an exaggerated (e.g., masculinized) early LH response to GnRHa testing in women with hyperandrogenic anovulation and congenital adrenal virilizing disorders suggest that events occurring before puberty, perhaps during fetal life, may irreversibly alter neuroendocrine function. Hyperinsulinemia from insulin resistance is an important regulatory mechanism governing ovarian hyperandrogenism. Hyperinsulinemia in hyperandrogenic anovulatory women potentiates ovarian hyperandrogenism by enhancing LH secretion; potentiating 17-hydroxylase and, to a lesser extent, 17,20-lyase activity; and suppressing SHBG capacity. It is a key component of hyperandrogenic anovulation caused by a type of insulin resistance that in independent and additive to that of obesity alone. Although the mechanisms governing insulin action on ovarian steroidogenesis are unknown, abnormalities of intracellular insulin signaling or cytochrome P450c 17[alpha] activity may render the 17-hydroxylase/17,20-lyase enzyme complex more sensitive to insulin. Hyperinsulinemia in hyperandrogenic anovulatory women is accompanied by upper-body obesity characterized by an increased amount of abdominal fat. Upper-body obesity is an important independent risk factor for CVD and diabetes. Although genetic and environmental factors affect fat distribution, sex steroids, particularly androgens, regulate lipid metabolism, suggesting yet another link between the hormonal and metabolic abnormalities of hyperandrogenic anovulation. A careful history and physical examination guide the extent of diagnostic testing. Slowly progressive hirsutism with anovulation of peripubertal onset usually reflects hyperandrogenic anovulation. This type of clinical presentation requires an evaluation to rule out other endocrinopathies (e.g., virilizing tumors, adult-onset CAH, hyperprolactinemia, and Cushing's syndrome). Virilization or severe rapidly progressive hirsutism requires immediate investigation to rule out a possible virilizing tumor. The ultimate goals of therapy for hyperandrogenic anovulatory women are to normalize the endometrium, antagonize androgen action at target tissues, reduce insulin resistance, and correct anovulation, if necessary.

Male gonadal function after chemotherapy in survivors of childhood malignancy.

Investigations of adult patients have shown that chemotherapy causes gonadal damage, but much less information is available about the impact of chemotherapy on gonadal function in children with malignant disease. At one time, being prepubertal during therapy was thought to confer some protection against chemotherapy induced gonadal damage. However, recent studies have indicated otherwise. We designed this study to assess gonadal function in 15 postpubertal males who had received polychemotherapy for a malignant disease during childhood and we compared them with 13 control adults males. The mean age of the patients at the time of the study was 18.2 +/- 3.6 years (range 13.8-29.0), and when given chemotherapy treatment was 10.2 +/- 3.0 years (range 6-16). At that time 12 were prepubertal and at the time of the study all were Tanner V. The mean interval from the completion of treatment until the study was 6.42 years (range 2.0-16.5). All patients had received polychemotherapy. We evaluated testicular size, sperm counts, LH and FSH after GnRH test, and testosterone levels. Puberty had progressed normally in all patients. We found no significant differences in testosterone and basal LH levels between patients and controls. However, we detected an appreciable difference in peak LH levels (P < 0.05) and in basal and peak FSH levels (P < 0.001). Seven patients had exaggerated LH response to GnRH, indicating dysfunction of the Leydig cells. The results of semen analyses were: 8 patients had azoospermia, 3 oligospermia, and 1 patient had a normal semen analysis. All patients with semen abnormalities presented a basal and peak FSH higher than the mean +2 SD of the control group. In summary, we found no evidence of gonadal protection in prepubertal patients. We found a high incidence of germinal cell damage, whereas Leydig cell abnormalities were found less often. An endocrine study of patients that have received chemotherapy is warranted.

Long-term naltrexone treatment normalizes the pituitary response to gonadotropin-releasing hormone in polycystic ovarian syndrome

To investigate the influence of opioid system on the exaggerated LH response to GnRH test in the polycystic ovarian syndrome (PCOS). Pituitary stimulation (GnRH 100 micrograms) in a group of PCOS patients under basal condition and after 4 weeks of treatment with naltrexone. In the PCOS group, the naltrexone treatment determines a significant reduction of the LH response (calculated as the area under curve) to GnRH test, with a similar significant decrease of the LH:FSH. Naltrexone normalizes in the PCOS group the pituitary response to GnRH test, abolishing every statistical differences with the control group.

Evidence of Endocrine Involvement Early in the Course of Human Immunodeficiency Virus Infection*

Adrenal, gonadal, and thyroid function were assessed in 40 asymptomatic subjects in whom infection with the human immunodeficiency virus (HIV) had recently been documented. None of the patients had historical or clinical evidence of endocrine dysfunction. Their mean serum hormone levels were also within the expected ranges, but several differences were noted compared to those of seronegative controls. Basal cortisol, basal aldosterone, and ACTH-stimulated cortisol were significantly lower in the HIV group. One subject (2.5%) had a subnormal cortisol response, and two (5%) had abnormal aldosterone responses to ACTH. PRA tended to be higher, and serum angiotensin-converting enzyme levels somewhat lower in the HIV group. Serum free testosterone was markedly elevated in the HIV patients and was associated with an exaggerated LH response to GnRH, but PRL, estradiol, and basal and peak GnRH-stimulated FSH did not differ between groups. Three subjects (8%) had subclinical hypothyroidism. Serum thyroid hormone levels were normal, but basal T3 was lower in the HIV group compared to control values. While of little immediate clinical importance, many subtle endocrine aberrations are evident very early in the course of HIV infection. These findings obtained in HIV-seropositive subjects without infections or tumors and who were not receiving medical therapy suggest an effect of HIV on each of the endocrine systems examined.

LH pulsatility and response to a single s.c. injection of buserelin in polycystic ovary syndrome

The present study was undertaken in order to determine whether patients with polycystic ovary syndrome (PCOS) have LH pulse frequency and/or amplitude higher than those in normal cycling women during the follicular phase, and, if so, to establish possible factors which might influence LH secretion in PCOS. The study was conducted on 14 PCO patients (aged 19-30 years), who were subdivided according to the data on their cycle abnormality into 2 groups: amenorrheic (Am-PCOS, n = 9) and oligomenorrheic (O-PCOS, n = 5). LH pulsatility was assessed in the early follicular phase in controls (n = 5) and O-PCOS and at any time in Am-PCOS. Blood samples were taken every 10 minutes for 4 hours. Pulse analyses of LH data were performed using the Munro program. The buserelin test was performed on the same day by injection of 40 micrograms of buserelin (blood samples were taken every 60 minutes for the following 10 hours). Eleven PCO patients and 12 control subjects had an oral glucose tolerance test (oGTT) (blood samples were taken every 60 minutes for glucose, insulin and C-peptide measurements). Both mean LH pulse frequency and mean pulse intervals were not distinguishably different in PCO women (Am and O) and controls. In contrast, the mean pulse amplitude was significantly higher in the Am-PCOS group than in O-PCOS women and controls (p less than 0.02 and p less than 0.001, respectively). A significant positive correlation was established between nadir LH concentrations and LH pulse amplitude (r = +0.966, p less than 0.001). The LH response to buserelin stimulation was significantly higher in Am-PCOS than in O-PCOS (p less than 0.004). A highly significant positive correlation was observed between LH pulse amplitude and insulin response during oGTT (p less than 0.001) in PCO subjects. Basal (prebuserelin) LH concentrations correlated significantly with fasting insulin levels (p less than 0.008) and insulin and C-peptide responses to oGTT. These results allow us to conclude the following: 1. An increased LH pulse amplitude and an exaggerated LH response to buserelin observed in amenorrheic PCO subjects compared to those in oligomenorrheic PCO subjects fail to support the hypothesis of an intrinsic hypothalamo-pituitary abnormality. 2. The relationship between fasting and glucose-stimulated insulin levels with LH nadir concentrations, pulse amplitude and response to buserelin suggests an etiological role of insulin in the pathogenesis of PCOS.

Familial Type C Syndrome of Insulin Resistance and Short Stature with Possible Autosomal Dominant Transmission.

We describe a 17-yr-old girl with insulin resistant diabetes, acanthosis nigricans, hirsutism and short stature. At the age of 14 she was found to have glycosuria and diagnosed as diabetes mellitus. No endocrinological abnormality except transient amenorrhea and exaggerated LH response to LHRH was found. Insulin resistance was demonstrated by fasting hyperinsulinemia, insulin tolerance test and euglycemic glucose clamp test, and large doses of insulin with CSII were not effective in controlling blood glucose. Insulin binding to erythrocytes was normal, suggesting a postbinding defect. The same phenotype of insulin resistant diabetes and short stature was found in her mother who was diagnosed as diabetes mellitus at the age of 31 and died of diabetic nephropathy at the age of 41. Her maternal grandfather and uncle were reportedly affected with the same phenotype. Her father had impaired glucose tolerance, but no hyperinsulinemia. Two sisters had essentially normal glucose tolerance. Insulin binding to erythrocytes of her father and mother was also in the normal range. These results suggest that the present case may be a rare syndrome present together with type C syndrome of insulin resistance, and with short stature which was inherited autosomal dominantly.

Hypothalamic hypogonadism following major head injury.

Endocrine studies, using the four hypothalamic releasing hormones, gonadotrophin releasing hormone, thyrotrophin releasing hormone, corticotrophin releasing hormone and growth hormone releasing hormone, were performed in 33 males after admission with a major head injury. The test was repeated 7 days later in all 33 patients and after 3-6 months in 21 patients. All patients had a period of unconsciousness followed by post-traumatic amnesia of greater than 24 h. The results obtained from investigating the gonadal axis are reported in this paper. The levels of total and free testosterone, basal FSH and basal LH fell significantly during the first 3 days after injury, when the LH and FSH responses to GnRH achieved their highest peak levels. This hormone pattern has not previously been reported in the gonadal axis and may be a consequence of hypothalamic dysfunction. The severity of the injury was negatively correlated to the testosterone concentration on admission and to the basal and peak FSH concentrations 1 week later. Persistent hypogonadism was found in five of the 21 patients retested after 3-6 months, with low testosterone concentrations and three continued to have an exaggerated LH response to GnRH. Thus major head injury frequently results in hypogonadism shortly after injury, with an increased gonadotrophin response to GnRH. In addition, a substantial minority of patients continue to be hypogonadal after 3-6 months. In view of these findings we strongly suggest that all patients should be endocrinologically assessed at intervals following severe head injury.

A longitudinal study on the prognosis of ovulatory disturbance in teenage patients with high LH and normal FSH serum levels

To study the prognosis of adolescent ovulatory disturbance in patients with persistently elevated LH levels (greater than or equal to 25 mIU/ml), normal FSH levels and high LH/FSH (greater than 2.0), 17 patients aged 12-19 years were studied longitudinally for 4-9 years. These 17 patients consisted of 7 patients suffering from amenorrhea with estrogenic effect, 5 patients with functional bleeding, 3 patients with delayed menarche and 2 patients with oligomenorrhea. All of the patients showed exaggerated LH responses to 100 micrograms of LHRH administration while the FSH responses were not different from those obtained from normal women. Out of the 17 patients, 10 (58.8%) patients showed the values of testosterone and 7 (41.2%) androstenedione which were above the mean + 2SD of normal women. Consequently, the mean serum testosterone and androstenedione levels were significantly higher than those in normal women. The mean LH (36.6 +/- 8.3 mIU/ml), FSH (11.2 +/- 1.5 mIU/ml) and LH/FSH (3.3 +/- 0.8) at the age of 21.4 +/- 2.5 years were not different from the mean LH (39.9 +/- 13.3 mIU/ml), FSH (10.8 +/- 1.8 mIU/ml) and LH/FSH (3.8 +/- 1.5) at the age of 16.1 +/- 1.8 years, respectively. None of the 17 patients showed amelioration or deterioration of ovulatory disturbance during long-term observation. To further investigate the central dopamine activity, 10 mg of metoclopramide (MCP) was administered intravenously in these 17 patients. The LH and PRL responses to MCP were evaluated, and the results were compared to those obtained from 17 patients aged over 20 with PCO and from 17 normal women. The LH responses to MCP were positive in this juvenile patient group and the patients aged over 20 PCO group. However, the LH responses to MCP were negative in normal women in both the follicular and luteal phases. In contrast, the PRL responses to MCP were significantly attenuated in juvenile patients and in patients aged over 20 with PCO compared to those in normal women. Since the hormonal profiles in these 17 patients with anovulation or oligo-ovulation were very similar to those in the group aged over 20 with established PCO, it may be suggested that 1) at least part of the adult patients with PCO may have had PCO from late adolescence; 2) the majority of the patients with high LH and normal FSH levels in adolescence will suffer from ovulatory disturbance continuously; 3) in these patients, an aberration of central dopamine in control of LH and PRL may exist.

Prolactin release in polycystic ovarian syndrome.

To evaluate the prevalence of hyperprolactinemia in patients with polycystic ovarian syndrome (PCO), 72 patients with oligo- or anovulation were studied. All of the patients had persisting elevated LH (greater than 25 mIU/ml), normal FSH, high LH/FSH ratio (greater than 2.5), and exaggerated LH responses to LHRH. Mean testosterone and androstenedione concentrations were appreciably increased in these patients. Out of 171 samples for prolactin (PRL) determination from these 72 patients, only 5 patients had a PRL value above 30 ng/ml during the first sampling. The next sampling from these same 5 women disclosed that they were transiently hyperprolactinemic because the next samples showed a normal PRL value. To further investigate the PRL secretory capacity 500 micrograms of TRH and 10 mg of metoclopramide (MCP) were administered to these 72 and 44 patients, respectively. The PRL response to MCP was significantly blunted in these patients compared to normal women while the PRL response to TRH in these patients was not indistinguishable from that in normal women. These results indicate that the true prevalence rate of hyperprolactinemia in PCO may be low rather than high and the association of hyperprolactinemia with PCO may be coincidental rather than a pathogenically related phenomenon.

The significance of small pulses of gonadotrophin-releasing hormone.

A series of experiments was conducted to ascertain the significance of 'small' pulses of gonadotrophin-releasing hormone (GnRH). In the first experiment, ovariectomized hypothalamo-pituitary disconnected (HPD) ewes were given 250 ng pulses of GnRH every 2 h for 1 week, 25 ng pulses every 2 h for 24 h, 25 ng pulses hourly for 24 h and then alternating hourly pulses of 25 and 250 ng. During the 25 ng pulses, LH was not detectable in plasma and FSH concentrations declined after 2 days. Following the 25 ng pulses, the resumption of 250 ng pulses led to exaggerated LH responses (mean +/- S.E.M. pulse amplitude 18.7 +/- 1.7 vs 10.2 +/- 1.2 micrograms/l in the first week). In a second experiment, ovariectomized-HPD ewes were maintained on 250 ng GnRH pulses every 2 h for 1 week and were then given three 25 ng pulses mid-way between the 250 ng pulses. Samples of blood were taken over three 250 ng pulses without 25 ng insertions and over three pulses with insertions. The insertion of 25 ng GnRH pulses did not cause LH pulses in their own right and did not alter the LH responses to the 250 ng pulses. In a third experiment, 50 ng GnRH pulses were inserted between the 250 ng GnRH pulses, as in experiment 2; these 50 ng pulses caused small LH pulses and led to a reduction in the response of the LH pulse amplitude to the 250 ng pulses. The 'small' LH pulses which occurred in response to 50 ng GnRH compensated for the reduced responses to the 250 ng pulses.(ABSTRACT TRUNCATED AT 250 WORDS)

439 MULTIPLE HORMONE RESISTANCE IN PSEUDOHYPOPARATHYROIDISM TYPE(PHP-1)

PHP-1 can be divided into 2 groups, with either diminished(A)or normal (B) G stimulatory regulatory protein activity(Gs) of the hormone receptor-adenylate cyclase system. In 14 PHP-1 patients (pts), aged 9 mos to 22 yrs we measured erythrocyte Gs protein activity and performed detailed endocrine evaluation for evidence of multiple hormonal dysfunction, as previously shown in PHP-1A adults (Am J Med 1983:74,545). Results: 6 pts had PHP-1A (↓Gs) and all had classical clinical features (Albright's Hered. Osteodyst.-AHO). In this group hypothyroidism was diagnosed in 2 neonates by thyroid screening (↑TSH) and 2 others had low/low N T4 & ↑TSH but neg. thyroid antibodies. All received L-thyroxine. Two girls had an exaggerated LH response to LHRH (Δmax 74 & 93.4 U/L),the first with delayed puberty and delayed menarche (21 yrs) Three pts, 2 with primary enuresis, had elevated AVP/plasma Osm ratios after water deprivation. Eight pts had PHP-1B, and only 1 had clinical features of AHO. Of 6 pts >11 yrs, 4 males had increased LH reserve (ΔLH 54, 59, 34.5, 85 U/L), but normal pubertal development. 4 pts had elevated AVP/plasma Osm ratio, 1 with primary enuresis. Conclusion:(1) AHO is a good clinical marker for PHP-1A in children (2) in PHP-1A, multiple hormone resistance of variable severity is common, with hypothyroidism, pubertal delay and nocturnal enuresis as presenting clinical features (3) In PHP-1B, evidence of mild hormonal resistance is occasionally present, despite normal erythrocyte Gs protein activity.

Pituitary responsiveness to gonadotrophin-releasing and thyrotrophin-releasing hormones in epileptic patients receiving carbamazepine or phenytoin.

Pituitary responsiveness to gonadotrophin-releasing (LHRH) and thyrotrophin-releasing (TRH) hormones was studied in 19 epileptic patients receiving long-term carbamazepine or phenytoin therapy and 14 normal control subjects. Baseline prolactin levels were normal in the patients; 2h after LHRH-TRH the prolactin levels in women on carbamazepine were significantly higher than in the controls, but apart from this, no other differences were found. Baseline LH levels were raised in male patients and the response to LHRH-TRH was exaggerated in all patients on carbamazepine. FSH levels were normal throughout. The exaggerated LH response is consistent with primary hypogonadism caused by enhanced sex hormone metabolism, secondary to hepatic enzyme induction by the antiepileptic drugs.

Gonadotropin, Prolactin, and Thyrotropin Secretion in Lepromatous Leprosy

Gonadotropin, PRL, and TSH secretion was determined in 14 patients (27 to 56 years of age) with lepromatous leprosy and in 28 controls. Each subject received LHRH (100 μg), TRH (200 μg), and the dopaminergic antagonist, metoclopramide (10 mg), at 30‐minute intervals, with periodic blood sampling. On the basis of the LH response to LHRH, the patients were divided into two groups. Group I consisted of nine patients with an exaggerated LH response to LHRH. The remaining five patients of Group II had a normal response to LHRH. Mean basal and peak FSH responses to LHRH were increased in both groups, but were greater in Group I. Mean 17β‐estradiol (E2) levels were increased in both groups, whereas, testosterone values were normal. Basal PRL levels were similar to those in controls, but there was an increased PRL response to both TRH and metoclopramide in Group I patients. In contrast, Group II patients had PRL responses identical to controls. Both groups had increased TSH responses to TRH in the presence of normal basal thyroxine (T4) and triiodothyronine (T3) levels. The PRL response to TRH correlated with both basal and peak FSH responses to LHRH, but not with LH, E2, nor testosterone. The TSH response did not correlate with either gonadotropins, E2, or thyroid hormone levels. Similar abnormalities in PRL and TSH secretion have been described in patients with primary testicular failure.

Restoration of oestrogen-positive feedback effect on LH release in women with prolactinoma by transsphenoidal surgery.

The effects of hyperprolactinaemia on the hypothalamo-pituitary axis by iv injection of 100 micrograms luteinizing hormone releasing hormone (LRH) in 7 women with prolactinoma before and 3 months after normalization of the Prl level by transsphenoidal surgery. A dose of 20 mg of conjugated oestrogen (Premarin) was also infected iv into patients with prolactinoma before and 4 months after surgery, and the serum LH levels were determined serially for 120 h after the injection. Surgical treatment caused significant reduction of the mean (+/- SE) serum prolactin (Prl) level from 123.3 +/- 7.8 to 19.4 +/- 5.6 ng/ml. But the differences in the basal levels of HL (11.3 +/- 2.2 to 8.6 +/- 1.5 mIU/ml), FSH (8.3 +/- 2.4 to 10.6 +/- 3.7 mIU/ml) and oestradiol (26.6 +/- 8.6 to 37.5 +/- 5.5 pg/ml) before and 4 months after surgery were not significant. An exaggerated LH response to LRH in untreated prolactinoma patients was also observed after surgical treatment. After surgical treatment, patients showed LH release with a peak between 48 and 72 h after the injection of Premarin, whereas before treatment they did not show any LH discharge. The mean percent increase in LH between 48 and 72 h was also significantly higher after operation than before operation. These results suggest that the hyperprolactinaemia in prolactinoma patients may cause an impaired positive feedback effect of oestrogen on LH release and that this derangement can be reversed by reduction of the Prl level by adenomectomy.

Thyrotropin-releasing hormone provokes abnormal follicle-stimulating hormone (FSH) and luteinizing hormone responses in men who have pituitary adenomas and FSH hypersecretion.

Serum FSH ad LH concentrations after the administration of TRH were measured in 10 men who had pituitary adenomas associated with FSH hypersecretion. Similar measurements were made in 12 men who had pituitary adenomas but no FSH hypersecretion, in 10 age-matched, normal men, and in 5 men who had primary hypergonadism. The mean serum LH concentration in the men who had pituitary adenomas and FSH hypersecretion increased 136% after TRH administration, significantly greataer (P < 0.005) than the 48% increase in the normal men or the 51% increase in the men who had pituitary adenomas without FSH hypersecretion. Serum LH did not increase at all in the men who had primary hypoganadism. The serum FSH concentration did not increase in any of the normal men, in the men who had pituitary adenomas without FSH hypersecretion, or in the men who had primary hypogonadism, but did increase in 5 of the 10 men who had FSH hypersecretion; the mean increase in these 5 men was 38%. The exaggerated LH responses and the nonspecific FSH responses to TRH of the men who had pituitary adenomas associated with FSH hypersecretion suggest that control of both FSH and LH secretion by these adenomas is abnormal and, therefore, that these adenomas are likely gonadotroph cell adenomas.

Dissociation of pituitary glycoprotein response to releasing hormones in chronic renal failure.

The LH, FSH and TSH response to LRH and TRH has been evaluated in patients with chronic renal failure. Basal gonadotrophins were elevated in 3 out of 6 males; one of 4 pre-menopausal females had increased basal LH. Exaggerated LH responses to LRH were noted in 4 out of 6 males and one of 4 females; FSH reponses were increased in 3 of these males. One male and one female had attenuated LH and FSH responses to LRH. Both testosterone and oestradiol levels were reduced. In 5 out of 6 subjects tested both pre- and post-dialysis there was a greater LH and FSH response to LRH following dialysis. This suggests the presence of a dialysable toxin which is inhibiting the gonadotrophin response to LRH. Gonadotrophin levels remained elevated during 4 h of dialysis suggesting prolongation of the metabolic clearance rate. Despite low T3 levels, TSH response to TRH (200 microgram) was only elicited in 2 of 6 cases. However, all 3 responded to 500 microgram and 2 out of 3 to 1000 microgram TRH, the third showing an attenuated response. TSH levels also remained persistently elevated in the responders. Dialysis however, failed to improve the relative TSH non-responsiveness to TRH. In conclusion the data has shown that there is a dissociation in glycoprotein hormone responses to releasing hormones in ureamia. Whereas the gonadotrophs retain their responsiveness to LRH, the thyrotrophs appear to be more effected by the uraemic process and demonstrate an impaired response to TRH.

Pituitary function following surgery for prolactinomas.

Preoperative and postoperative endocrine function studies were performed in 18 patients with prolactin-secreting tumors defined by hyperprolactinemia and abnormal sellar tomography. Preoperative testing showed decreased prolactin response to thyrotropin-releasing hormone (TRH); 9 of 18 patients had low basal serum LH and 11 of 15 patients had low urinary LH. In most patients follicle-stimulating hormone (FSH) was normal (serum, 13/18 and urine, 13/13). Five of 9 patients tested with luteinizing hormone-re-leasing hormone (LH-RH) had an exaggerated LH response and the rest were normal. The changes in gonadotropin secretion did not correlate with tumor size. In contrast, only patients with suprasellar extension showed deficiencies of thyroid hormone, or insulin-stimulated growth hormone (GH) or cortisol. Following surgery, 10 of 18 patients had normal serum prolactin. However, the prolactin response to TRH remained abnormal in 10 of 11 patients tested. Serum LH increased to normal in all patients whose prolactin values reverted to normal postoperatively. The GH values following provocative testing were higher postoperatively in the group as a whole and normalized in the patients with low GH values preoperatively. Clinical response did not correlate with tumor size; 3 of 5 patients with microadenomas recovered normal menses, while 5 of 8 patients with larger tumors resumed menses. Several of our findings may bear on the pathophysiology associated with these tumors. First, the TRH test results suggest that disordered prolactin secretion may persist after tumor removal. Second, the hypogonadotropic state in these individuals seems to represent a hypothalamic rather than a pituitary defect, ie, the defect is observed in patients with small tumors, and pituitary responsiveness to LH-RH is normal or exaggerated. The resolution of clinical hypogonadism and disordered LH secretion after surgery is consistent with a direct effect of prolactin on the hypothalamic control of LH secretion.

GONADOTROPHIN, THYROTROPHIN AND PROLACTIN RESERVE IN β THALASSAEMIA

Gonadotrophin (Gn), thyrotrophin (TSH) and prolactin (PRL) reserve was evaluated in patients (aged 12-26 years old) with beta thalassaemia. Abnormalities were detected in Gn reserve only. When compared with young adult controls, three of the four female patients and one of the two adult males had markedly impaired Gn responses to LH-releasing hormone (LHRH). Of the five prepubertal males, one had no Gn rise following LHRH, while responses in the other four patients were comparable to those in boys with delayed puberty. Only one adult male had an exaggerated LH response to LHRH. TSH and PRL dynamics were normal. No correlation could be found between the severity of the disturbance in the gonadal axis and the total number of blood transfusions. Our findings correlate best with the severity of the disease process itself.