The combined pituitary function test in children: an evaluation of the clinical usefulness of TRH and LHRH stimulation tests through a retrospective analysis of one hundred and twenty six cases

OBJECTIVE: The combined pituitary function test is routinely used in the endocrine investigation of short children. The TRH and luteinising hormone-releasing hormone (LHRH) response tests have been shown to be of minimal value in adults. We have evaluated the clinical utility of these tests in the context of combined pituitary function testing in children. DESIGN: A retrospective analysis of basal hormone measurements and pituitary stimulation tests in relation to clinical assessment of pituitary function. PATIENTS: One hundred and twenty-six children, 82 boys and 44 girls, aged 2-17 years, who had undergone pituitary function testing were studied. RESULTS: The TSH response to TRH stimulation correlated directly with basal plasma TSH but not basal plasma total T4. In patients with an impaired response to stimulation, basal TSH concentrations were <2.0 mIU/l and significantly lower than in patients with a normal response (P < 0.0001). An impaired response to TRH stimulation had a positive predictive value of 0.43 and a negative predictive value of 0.90 for the diagnosis of hypopituitarism. A basal TSH concentration of <2.0 mIU/l had a positive predictive value of 0.22 and a negative predictive value of 0.92. A low basal T4 (normal range 60-140 nmol/l) in combination with an inappropriately low or normal basal TSH was always associated with a diagnosis of hypopituitarism. The responses of plasma LH and FSH to LHRH stimulation correlated directly with basal plasma LH and FSH concentrations. Basal gonadotrophin concentrations, basal sex hormone concentrations or response to LHRH stimulation could not distinguish patients with constitutional delay of growth and puberty from those with hypopituitarism. There was no apparent relationship between either basal gonadotrophin concentrations or response to LHRH stimulation and clinical assessment of pituitary function. In patients > or =13 years with constitutional delay of growth and puberty the median and interquartile ranges of basal LH and FSH were 1.4 IU/l (0.7-3.6) and 2.6 IU/l (2.2-5.2) respectively. The three hypopituitary patients in this study with chronological age > or =13 years had undetectable concentrations of both gonadotrophins. The response of LH and FSH to LHRH stimulation was significantly lower in patients > or =13 years with clinical hypopituitarism than in those with intact pituitary function (P <0.02). CONCLUSION: TRH and LHRH tests in children with short stature appear to have little value over and above the baseline hormone measurements. An abnormal response to hormone stimulation is not diagnostic of hypothalamic-pituitary disease. We have demonstrated that neither TRH nor LHRH stimulation tests should be routinely used in the investigation of children with short stature.     

Effects of starvation in rats on serum levels of follicle stimulating hormone, luteinizing hormone, thyrotropin, growth hormone and prolactin; response to LH-releasing hormone and thyrotropin-releasing hormone.

Adult male Sprague-Dawley rats averaging 300 g each were subjected to complete food removal for 7 days (acutely starved), 7 days complete food removal followed by 2 weeks of 1/4 ad libitum food intake (chronically strved), 7 days complete food removal and 2 weeks of 1/4 ad libitum intake followed by ad libitum feeding for 7 days (refed), or fed ad libitum throughout (controls). Serum LH, FSH, TSH, PRL, and GH levels were measured by radioimmunoassays for each group of rats. The in vivo response to the combination of synthetic LHRH and TRH also was tested in each group of rats. Circulating LH, TSH, GH, and PRL were significantly depressed in acutely and chronically starved rats, and FSH was lowered only in acutely starved rats. After 7 days of refeeding, serum levels of LH and FSH were significantly greater than in ad libitum fed controls, PRL returned to control levels, and TSH and GH increased but were still below control levels. After LHRH + TRH injection serum LH and TSH were increased significantly in all groups of rats, FSH and PRL rose in acutely but not in chronically starved rats, and GH was not elevated in any group. The increases in serum LH, FSH, TSH and prolactin in response to LHRH + TRH injection in acutely or chronically starved rats were equal to or greater than in the ad libitum fed controls. These data indicate that severe reductions in food intake result in decreased release of at least 5 anterior pituitary hormones, and this is due primarily to reduced hypothalamic stimulation rather than to inability of the pituitary to secrete hormones.     

Selectivity of melatonin pituitary inhibition for luteinizing hormone-releasing hormone

The pineal indole melatonin suppresses the neonatal rat luteinizing hormone (LH) and follicle-stimulating hormone (FSH) responses to LH-releasing hormone (LHRH), as shown in previous studies from this laboratory. We show in this study that the melatonin inhibition is a selective effect and is not due to general inhibition of pituitary function. The effects of the indole on the responses to thyrotropin-releasing hormone (TRH) and somatostatin (SRIF) and on basal pituitary hormone secretion were examined with cells in culture. Neonatal rat anterior pituitary cells dissociated with collagenase and hyaluronidase were cultured overnight and distributed to 35-mm dishes at the time of use. For examination of melatonin effects on the response to releasing hormones, the cells were incubated for 3 h in control medium or medium containing LHRH (10-9-10-6 M), TRH (10-10-10-6 M), or SRIF (10-9-10-6 M), either alone or in the presence of melatonin (10-8 or 10-6 M). For examination of basal hormone secretion, the cells were incubated for 1.5, 3, 6, 15, or 24 h in either medium alone or medium containing melatonin (10-6 M). Medium and cell lysate concentrations of LH, FSH, thyroid-stimulating hormone (TSh), prolactin (PRL) and growth hormone (GH) were determined by double antibody RIA. As previously, melatonin (10-8 M) significantly suppressed LH and FSH release by all concentrations of LHRH. This concentration of the indole produced maximal suppression of both LH and FSH responses to LHRH. By contrast, melatonin at a 100-fold greater concentration (10-6 M) had no effect on TRH stimulation of TSH or PRL release or on SRIF inhibition of GH release. Similarly, melatonin had no effect on basal release of TSH, PRL, or GH at the times examined. These findings show that melatonin inhibition of the gonadotroph response to LHRH is a selective effect.     

PITUITARY FUNCTION TESTS IN SHEEHAN'S SYNDROME

Fourteen patients with a typical history of Sheehan's syndrome underwent pituitary function tests with simultaneous injections of 100 μg LH-RH, 200 μg TRH and 0·05–0·1 units of soluble insulin per kg body weight. Serum prolactin levels remained unchanged in all of eleven subjects given TRH. GH levels did not rise after hypoglycaemia in five subjects. In contrast serum LH and FSH rose significantly in twelve out of fourteen subjects given LHRH and serum TSH rose significantly in five out of seven subjects given TRH. It is concluded that pituitary function is relatively preserved for LH and FSH but not for prolactin and GH in Sheehan's syndrome. It is further suggested that absence of a rise in prolactin following TRH stimulation may provide the most sensitive test of pituitary hypofunction in postpartum haemorrhage.     

Influence of estrogens on pituitary responsiveness to LHRH and TRH in human (author's transl)]

Estrogens are supposed to be responsible for the increased sensitivity of the pituitary to LHRH and TRH observed in female in comparison to male adults. The influence of physiological and pharmacological variations of estrogens was studied throughout female life. Adolescents girls showed enhanced responses to both LHRH and TRH, as compared to cycling adult women. The adolescent pituitary seems to be particularly sensitive to the increasing estradiol secretion. Adult cycling women disclosed higher LH and FSH responses to LHRH during the periovulatory and luteal phases than during the follicular phase; prolactin response to TRH was enhanced only during the periovulatory phase while TSH response remained constant throughout the menstrual cycle. In adult women, sequential oral contraceptives increased LH, FSH and prolactin responses to LHRH and TRH while TSH response was unchanged. Combined contraceptives displayed an important inhibition of the LH, FSH and TSH responses but not of that of prolactin. The inhibitory effects on gonadotrophins and TSH may be due to the association of gestagens to estrogens. Postmenopausal women presented a TSH response to TRH similar to that found in male adults while prolactin response remained unchanged in spite of decreased basal values. The potentiatory effects of estrogens on the pituitary responsiveness to LHRH and TSH may be attributed either to an increased number or to an enhanced binding activity of the pituitary receptors to LHRH and TRH, as suggested by several experimental data.     

GH, ACTH, TSH, LH, and FSH reserve in pre pubertal girls with congenital adrenal hyperplasia.

The pituitary reserve of GH, ACTH, TSH, LH, and FSH was determined in seven prepubertal birls suffering from congenital adrenal hyperplasia due to 21-hydroxylation defect and under treatment with cortisone acetate. GH and ACTH were studied during the insulin induced hypoglycemia test. The LH, FSH, and TSH reserved were assayed by means of the LH-RH and TRH tests. GH behavior proved to be similar to that found in normal subjects, whereas basal and/or after stimulus ACTH turned out to be higher than the upper limits of the normal range in five out of six girls. The mean basal value and the mean LH peak were not significantly higher than those found in normal prepubertal girls; the mean basal value and the mean FSH peak were lower than the mean of the control group. The difference is significant (P less than 0.05) only between the peak values. The mean basal TSH in the patients is significantly higher (P less than 0.01) than the mean value of the control group. The maximum TSH after TRH is not significantly different from the mean value fo the control group.     

The hormonal status of patients with benign prostatic hypertrophy: FSH, LH, TSH and prolactin responses to releasing hormones.

In order to determine whether the benign prostatic hypertrophy (BPH) adenoma is responsible for low serum LH levels in patients with this disease, we measured FSH, LH and prolactin in sera collected from patients before and 0.8–2.2 years after retro-pubic prostatectomy, but found no change in their levels. Pituitary stimulation tests were therefore conducted to evaluate the pituitary hormone reserve in normal elderly men, and BPH patients before and after removal of the BPH adenoma. Blood was drawn 20 min before and during the administration of 100 μg LHRH and 200 μg TRH, as a single intravenous injection, and after 20, 60 and 120 min. Serum FSH, LH, TSH and prolactin were estimated by radioimmunoassays. Prior to prostatectomy, patients with BPH had significantly lower levels of serum LH, but not FSH, TSH or prolactin, as compared to normal men 20 min before the test. Serum LH in the BPH group after prostatectomy (1–2.75 years) was not statistically different from that of normal age-matched men, but the mean level more closely resembled that of the untreated BPH group. Although there were no significant differences in serum levels of FSH or prolactin between subject groups during stimulation, levels of LH and TSH in untreated BPH patients' serum were significantly lower than those of normal men. The BPH patients after prostatectomy resembled the normal men under these circumstances, and the serum levels of TSH in these ex-BPH patients were significantly higher than in untreated BPH patients. Similarly, the maximum LH and TSH responses to the hypothalamic releasing hormones were also significantly lower in the BPH patients as compared to normal age-matched men, and evidently return to normal 1–2.75 years after prostatectomy. No statistically significant differences were observed in the FSH and prolactin responses to LHRH and TRH between groups. The results suggest that a factor originating from the BPH adenoma, such as 5α-dihydrotestosterone, may be responsible for the suppression of pituitary LH and TSH responses to LHRH and TRH, respectively. It also appears that the pituitary of BPH patients does not regain its full secretory potential after the BPH adenoma has been removed, or that an additional factor may regulate pituitary LH secretion in the untreated and ex-BPH patients at the hypothalamic level.     

Possible altered dopaminergic modulation of pituitary function in normal-menstruating women with insulin dependent diabetes mellitus (IDDM)

In order to assess whether a possible altered dopamine activity in normal-menstruating diabetic patients may influence the pituitary hormone secretion we have measured the basal serum concentrations of Prl, LH and FSH in 28 patients with insulin dependent diabetes mellitus (IDDM) and in 55 normal-menstruating women at day 3 to 6 of the menstrual cycle. In addition basal levels of oestradiol-17 beta, TSH, thyroxine (T4), triiodothyronine (T3) and resin-T3 uptake (RT3U) were determined in 17 patients with IDDM and in 17 controls. The responses of FSH, LH, Prl, GH and TSH to metoclopramide (MTC) administration (10 mg iv) were studied in 17 patients and 17 controls. In 10 patients with IDDM and 8 controls the short-term variations in pituitary hormones and blood glucose concentration were evaluated. Patients with IDDM had significantly lower basal levels of Prl (P less than 0.01) and TSH (P less than 0.05) and significantly (P less than 0.05) higher basal levels of GH than normal women. No significant (P greater than 0.05) differences were found regarding basal serum concentrations of FSH, LH, oestradiol, T4, T3 and RT3U. During the 3 h period the mean coefficient of variation of Prl, FSH, LH and GH was not significantly (P greater than 0.05) different between diabetic patients and controls. Both groups responded significantly (P less than 0.01) in Prl and TSH to MTC but the TSH response was significantly (P less than 0.05) lower in patients with IDDM. The Prl response to MTC was not significantly (P greater than 0.05) different within the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of Synthetic Thyrotrophin Releasing Hormone (TRH) in Man

Summary: Synthetic TRH (200 μ g) administered intravenously to twelve normal subjects produced a consistent rise in serum thyrotrophin (TSH) levels reaching a peak 20 – 30 mins following the injection. No reproducible effects were seen on plasma levels of GH, LH, FSH or 11 -hydroxycorticoids measured concomitantly with TSH. Mean free thyroxine index following TRH rose by 23% at 60 and 120 mins. Two subjects treated with triiodothyronine and 17 untreated thyrotoxic patients showed marked impairment of TSH response to TRH. Reduced or absent TSH responses were likewise observed in five euthyroid patients with Graves' disease, two with ophthalmopathy as the sole manifestation of the disease. In ten patients with primary hypothyroidism, synthetic TRH evoked further increases of elevated basal TSH levels with exaggerated over-all responses. Five of seven euthyroid patients with pituitary tumours showed blunted TSH responses whereas all six patients with secondary hypothyroidism (resulting from pituitary or suspected hypothalamic lesions) exhibited normal or slightly exaggerated responses.
It is concluded that synthetic TRH is a specific stimulus to pituitary TSH release with considerable potential in the diagnosis of mind disturbances of thyroid function. Its use should promote better understanding of hydothalamic-pituitary-thyroid relationships.     

Hypothalamic-pituitary function in growth hormone-deficient patients with pituitary stalk transection

We compared 1.5 T magnetic resonance (MR) image findings with hypothalamic-pituitary function in 11 patients with idiopathic pituitary dwarfism, each of whom had a history of perinatal abnormalities, and 1 patient with posttraumatic pituitary dwarfism. MR imaging revealed transection of the pituitary stalk in all patients and the formation of an ectopic posterior lobe at the proximal stump in 9 patients, none of whom had polydipsia or polyuria. Three patients without an ectopic posterior lobe had diabetes insipidus. The 5 patients who had small pituitary glands (less than 2 mm in height) had hypothyroidism with low serum TSH concentrations and low serum cortisol responses to insulin-induced hypoglycemia; however, 7 patients with normal-sized pituitary glands had normal thyroid and adrenal function. The serum GH response to GHRH did not correlate with the size of the pituitary gland. The patients with small pituitary glands had delayed or prolonged serum TSH responses to TRH and impaired serum LH and FSH responses to GnRH; 4 of the patients with normal-sized pituitary glands had normal serum TSH, LH, and FSH responses. Only 2 patients had high basal serum PRL concentrations. The endocrinological data suggest that reestablishment of the hypothalamo-hypophyseal portal circulation, which cannot be seen by MR imaging, may occur. We suggest that the primary cause of idiopathic pituitary dwarfism in many patients is injury to the pituitary stalk at birth.     

Evidence for a thyrotropin inhibitory effect of histamine in man.

Because of certain side effects of cimetidine therapy which may be hormonally mediated (e.g. gynecomastia), there has been recent interest in the possible endocrine effects of this H2 histamine receptor-blocking agent used in the treatment of peptic ulcer disease. Accordingly, the effect of chronic cimetidine therapy on anterior pituitary function was examined in 12 adult men with mild peptic ulcer disease. TRH and insulin-hypolycemic stimulation tests were performed by standard methods. Serum for TSH and PRL RIA was obtained after TRH; serum for GH, cortisol, and PRL RIA was obtained after insulin-induced hypoglycemia. In addition, serum for LH, FSH, testosterone, and PRL was obtained every 4 h for 24 h. After these baseline studies, 300 mg cimetidine were administered orally 4 times a day for 4--8 weeks and the studies were repeated as before. Chronic treatment with cimetidine caused a significant increase in the peak TSH response to TRH at 30 min (mean peak TSH value before cimetidine, 7.0 microU/ml; after cimetidine, 10.2 microU/ml; P less than 0.05) as well as a significant increase in the TSH area under the curve. There was no statistically significant effect of cimetidine on basal TSH or basal or stimulated PRL secretion. Cimetidine had no effect on the GH, PRL, or cortisol response to insulin-induced hypolycemia or the 24-h secretion of LH, FSH, testosterone, or PRL.     

PROLACTIN, TSH, LH AND FSH RESPONSES TO A COMBINED LHRH/TRH TEST AT DIFFERENT STAGES OF THE MENSTRUAL CYCLE

A combined test with LHRH and TRH was investigated in the normal female subject during the menstrual cycle. LH and FSH responses were not affected by raised prolactin or TSH levels after TRH.
No correlation was seen between either basal levels or responses of prolactin and TSH after TRH, and no difference in responses on days 4 or 24 were observed. The increments in prolactin and TSH were significantly greater in female than in male subjects.
Although FSH responses to LHRH+TRH were not significantly different, LH responses on day 24 were greater than on day 4. A significant linear correlation between FSH and LH responses to LHRH was seen.
The results indicate that prolactin and TSH responses to TRH are greater in female than male subjects and that changes in LH and FSH after LHRH do affect these responses. Normal ranges for hormone responses after LHRH and TRH are defined.     

THE EFFECT OF LISURIDE HYDROGEN MALEATE, AN ERGOT DERIVATIVE ON ANTERIOR PITUITARY HORMONE SECRETION IN MAN

The effects of single oral doses of 0.2 mg of lisuride hydrogen maleate, a semisynthetic ergot derivative, on serum levels of prolactin (PRL), growth hormone (GH), thyroid stimulating hormone (TSH), luteinizing hormone (LH), follicle stimulating hormone (FSH), cortisol and blood glucose were studied in six normal males. Lisuride effectively inhibited basal PRL secretion as well as the PRL response to TRH given 3 h later. In addition, the drug raised basal GH levels and decreased basal and TRH stimulated TSH secretion. No significant differences between lisuride and control were observed in basal LH and FSH, LHRH stimulated gonadotrophins or in cortisol. Drowsiness was noted by all subjects, one became nauseated and another vomited, 60 and 90 min respectively after administration of lisuride. No changes were seen in pulse rate and blood pressure. The endocrine effects of lisuride were attenuated by the prior administration of the dopamine antagonist metoclopramide. These results suggest that lisuride acts as a long-acting dopamine agonist and that therefore this drug could be of therapeutic use in hyperprolactinaemic states and acromegaly.     

Hypogonadotropic hypogonadism in severe beta-thalassemia: effect of chelation and pulsatile gonadotropin-releasing hormone therapy

We studied pituitary-gonadal function in 11 male and 5 female patients, aged 12-30 yr, with severe beta-thalassemia and chronic iron overload. All had normal basal serum cortisol, T4, and PRL concentrations and normal serum cortisol and GH responses to insulin-induced hypoglycemia and TSH responses to TRH. Of the 11 male patients (all over 17 yr of age), only 3 attained full pubertal development and 4 had subnormal serum LH and FSH responses to GnRH. As a group, their mean basal serum testosterone (T) level was low [11.7 +/- 4.9 (+/- SE) nmol/L; normal, 10-40 nmol/L], and 9 of the 11 male patients responded to hCG with a rise in serum T. Two of the 3 female patients over 17 yr of age were prepubertal with undetectable serum estradiol (E2) levels and absent serum LH and FSH responses to GnRH; the other female patient had regular menstrual cycles and normal serum E2 levels and LH and FSH responses to GnRH. Six of the prepubertal patients (4 males and 2 females, aged 17-30 yr) were studied serially for 3 yr after the start of chelation therapy. Despite a fall of median serum ferritin from 11,910 to 1,303 pmol/L, there was no progression of puberty, and their basal and GnRH-stimulated serum LH and FSH and serum T or E2 levels did not change. Three of these patients (1 male and 2 female) then received pulsatile sc GnRH therapy in addition to chelation therapy for 6 months with no improvement. We conclude that chronic iron overload in patients with severe thalassemia leads to variable degrees of hypogonadotropic hypogonadism, which do not respond to chelation therapy given late in the course of the disease. The hypogonadism in most patients was due to pituitary hyporesponsiveness to GnRH.     

GONADOTROPHIN AND ALPHA SUBUNIT SECRETION BY HUMAN ''FUNCTIONLESS'' PITUITARY ADENOMAS IN CELL CULTURE: LONG TERM EFFECTS OF LUTEINIZING HORMONE RELEASING HORMONE AND THYROTROPHIN RELEASING HORMONE

The long-term effects of LHRH and TRH on gonadotrophin alpha subunit, FSH and LH secretion by cell cultures of four human chromophobic pituitary tumours have been examined. The tumours derived from one male and three female patients who presented because of visual disturbance but had no evident endocrine symptoms. Subsequent serum hormone analysis showed the FSH to be high in the male but low or normal in the post-menopausal females whereas LH levels were low in all patients. In culture, basal hormone secretion could be maintained for periods up to 63 d. All tumours secreted alpha subunit and FSH, but much lower amounts of LH. Addition of LHRH or TRH for a period of 12 to 41 d showed that alpha subunit, FSH and LH secretion were stimulated by LHRH from one tumour, by LHRH and TRH from two tumours. There was always a rapid decline in the LH secretion. The tumour which secreted FSH predominantly was stimulated by TRH. We conclude that human pituitary 'functionless' adenomas can secrete gonadotrophin alpha subunit and FSH in vitro and that secretion can be stimulated during long term releasing hormone experiments. LH secretion, however, cannot be maintained.     

Conventional pituitary irradiation is effective in lowering serum growth hormone and insulin-like growth factor-I in patients with acromegaly

BACKGROUND: There has been recent controversy as to the effectiveness of conventional pituitary irradiation in reducing circulating GH levels to less than 2.5 ng/ml and/or normalization of serum IGF-I. OBJECTIVES: Our objectives were to determine the effects of conventional pituitary irradiation on 1) lowering of serum GH and IGF-I levels, 2) the proportion of patients who achieve a GH level less than 2.5 ng/ml and a normal age-corrected IGF-I and the time taken to achieve this, and 3) the incidence of hypopituitarism and other adverse effects. DESIGN: We conducted retrospective data collection from 14 centers throughout the United Kingdom. PATIENTS: We studied 1840 patients with acromegaly, of whom 884 had received conventional pituitary irradiation. MEASUREMENTS: We assessed circulating GH and IGF-I levels and pituitary function at intervals after irradiation. RESULTS: Mean GH levels declined from 13.5 to 5.3 ng/ml at 2 yr after irradiation, to 2.0 ng/ml by 10 yr, and to 1.1 ng/ml at 20 yr. Twenty-two percent of patients achieved a level less than 2.5 ng/ml by 2 yr, 60% by 10 yr, and 77% by 20 yr. The interval to achieve this depended on the preirradiation GH level. IGF-I levels fell in parallel to those of GH with 63% of patients having a normal level by 10 yr. The proportions of patients with new pituitary hormone deficiencies 10 yr after irradiation were 18% for LH/FSH, 15% for ACTH, and 27% for TSH. No other side effects were noted. CONCLUSIONS: In this, the largest series reported, conventional pituitary irradiation is shown to be an effective and safe means of reducing both serum GH and IGF-I concentrations in patients with acromegaly.     

Combined pituitary stimulation test: interactions of hypothalamic releasing hormones in man

The use of hypothalamic releasing hormones for the clinical assessment of anterior pituitary function is both simple and free of severe side effects. Tests with the recently discovered substances GRF and CRF as well as with combinations of several releasing hormones are therefore used in many clinics. A reliable interpretation of such combined tests, however, is only possible when positive or negative interactions between these releasing hormones are known. After a rest of 2 h to reach basal cortisol levels, 7 groups of 5 male volunteers each received an iv bolus injection consisting of either: A): GRF (100 micrograms) + CRF (50 micrograms) + TRH (200 micrograms) + LHRH (100 micrograms), B): CRF + TRH, C): GRF + TRH, D): LHRH + TRH, E): TRH, F): GRF, G): CRF. During the following 2 h, GH, TSH, cortisol, LH, FSH and prolactin were measured every 15 min. The TSH response after the injection of all 4 releasing hormones was significantly higher (delta TSH = 16.5 +/- 2.0 microU/ml, x +/- SE) compared to the injection of TRH alone (delta TSH = 9.3 +/- 1.4 microU/ml; p less than 0.025). This increment in TSH secretion was confirmed when 2 groups of 5 female volunteers were studied with the TRH-test (delta TSH = 9.9 +/- 1.8 microU/ml) or the combination of all four releasing hormones (delta TSH = 16.8 +/- 2.9 microU/ml; p less than 0.05). This exaggerated TSH-response to TRH was demonstrated to be entirely due to simultaneous administration of GRF, whereas CRF and LHRH in combination with TRH had no additional effect on TSH release.(ABSTRACT TRUNCATED AT 250 WORDS)     

Reversible hypopituitarism in patients with large nonfunctioning pituitary adenomas

Detailed pituitary function studies were conducted on 26 patients with large nonfunctioning pituitary adenomas before and 2-3 months after transsphenoidal adenomectomy. Basal serum PRL, GH, TSH, LH, FSH, and ACTH levels were measured, and dynamic studies of their secretion were made. Preoperatively, GH deficiency was found in all 26 patients (100%), hypogonadism in 25 patients (96%), hypothyroidism in 21 patients (81%), and adrenal insufficiency in 16 patients (62%). Serum PRL levels were low (1.5-4 ng/ml) in 5 patients, normal (5-20 ng/ml) in 9 patients, and mildly elevated (21-53 ng/ml) in the remaining 12 patients. After selective adenomectomy, variable improvement in pituitary function occurred in 17 patients, worsening in 1 patient, and persistence of hypopituitarism in 8 patients. After surgery, normal thyroid function was documented in 12 of the 21 patients (57%) who were hypothyroid preoperatively. Similarly, 6 of the 16 patients (38%) with adrenal insufficiency recovered normal adrenal function, and 8 of the 25 patients (32%) with hypogonadism recovered normal gonadal function. GH deficiency persisted in all but 4 patients (15%). Serum PRL levels decreased in all patients, and only 5 had midly elevated levels after surgery. The presence of a normal or mildly elevated serum PRL level before surgery in these patients was of value in predicting possible recovery of pituitary function after surgery; none of the 5 patients with low preoperative serum PRL levels had any improvement in pituitary function after surgery. A rise in serum TSH levels after TRH administration before surgery also was helpful in predicting possible recovery from hypopituitarism. Most patients who had a rise in serum TSH level in response to TRH stimulation preoperatively recovered some pituitary function after adenomectomy. In contrast, no improvement in pituitary function occurred in patients who had blunted responses to TRH preoperatively. Improvement in pituitary function occurred more often in patients with tumors measuring 25 mm or less than in those with larger tumors. In conclusion, significant improvement in pituitary function may occur after surgical adenomectomy for nonsecreting pituitary tumors. A rise in serum TSH levels in response to TRH stimulation preoperatively suggested the presence of viable pituitary tissue in these patients with hypopituitarism. The presence of a normal or mildly elevated serum PRL level before surgery also suggested the presence of functioning pituitary lactotrophs. These observations suggest that compression of the portal circulation is a possible mechanism for hypopituitarism in this setting.(ABSTRACT TRUNCATED AT 400 WORDS)     

Multiple abnormalities of anterior pituitary hormone secretion in association with pseudohypoparathyroidism

A male with pseudohypoparathyroidism presented with several hormonal abnormalities. He was clinically euthyroid with no palpable goiter, His serum T4, total T3, T3 Sephadex retention, and 131I uptake were normal. However, elevated basal TSH levels and exaggerated TSH responses to TRH which normalized during the administration of thyroid extract suggested reduced thyroidal reserve. Despite these finding the 131I uptake increased after exogeneous TSH, and the T3 level rose after TRH. Basal testosterone levels and response to hCG were normal however, gonadotropins were elevated and there was an exaggerated response after LRH treatment. Both LH and FSH levels were suppressed by testosterone propionate. The patient demonstrated intermittent basal hyperprolactinemia and impaired PRL responsiveness after metolopramide, chlorpromazine, and insulin administration. There was, however, an intact response to TRH. Basal PRL, TSH, and LH levels decreased after the administration of L-dopa and bromocriptine. Although the precise mechanism underlying these finding is unknown, the elevated basal levels of TSH, LH, and FSH and the exaggerated responses to their respective releasing hormones suggest the presence of partial degree of end-organ resistance to these pituitary trophic hormones. Together with the resistance to PTH, this may imply a common defect, presumably at a postreceptor level. However, hyporesponsiveness of PRL to metoclopramide and chlorpromazine and normal responsiveness to TRH suggest that an abnormality of dopamine tone also exists in pseudohypoparathyroidism.     

SPECIFIC CONTROL OF FOLLICLE STMULATING HORMONE IN THE MALE: POSTULATED SITE OF ACTION OF INHIBIN

Serum luteinizing and follicle stimulating hormone concentrations were related to gonadal function, as reflected by sperm count and serum testosterone concentrations, in a group of men studied over 10 years after surgical correction of bilateral cryptorchidism in childhood. The results indicated that while all degrees of gonadal function occurred in these patients, the main adverse effect of cryptorchidism was on spermatogenesis. In some of the patients with oligospermia and normal Leydig cell function there was an isolated increase of basal serum FSH concentrations, suggesting a specific impairment of the testicular production of 'inhibin'. Gonadotrophin releasing hormone (LHRH) tests in these patients were compared to those in patients with normal basal gonadotrophins and to those with elevated basal LH and FSH concentrations. A selective exaggeration of the FSH response to exogenous LHRH in the group of patients with a monotropic elevation of FSH concentrations suggests that 'inhibin' modulates the secretion of FSH by an action on the pituitary rather than by modifying endogenous LHRH production by the hypothalamus.