[Proceedings: Anterior pituitary function test in pituitary tumors (or tumors of adjacent tissues). 2].
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The preferred method(s) and timing for retesting of the growth hormone (GH) axis in young adults with childhood-onset GH deficiency during the transition period are less well characterized than those for children and older adults. Retesting of other hypothalamic-pituitary axes for which replacement therapy had (e.g., thyroid hormone) or had not been (e.g., glucocorticoids and sex steroids) initiated in childhood also requires periodic reassessment. The transition period in children with hypopituitarism also represents the time for initiation of plans for transfer of care to an internist-endocrinologist with expertise in the management of hypothalamic-pituitary disease in young adults.
We examined 8 normal subjects and 16 patients with non-functioning pituitary tumors with a combined anterior pituitary test to evaluate the clinical usefulness of the test. Diagnoses included 9 of chromophobe adenoma, 3 of craniopharyngioma, 2 of Rathke's cleft cyst, and 1 each of intrasellar cyst and tuberculum sella meningioma. All subjects received hypothalamic releasing hormones: 1 micrograms/kg corticotropin releasing hormone (CRH), 1 micrograms/kg growth hormone releasing hormone (GRH), 500 micrograms thyrotropin-releasing hormone (TRH), 100 micrograms luteinizing hormone releasing hormone (LH-RH), and a relatively small dose (5 mU/kg) of lysine vasopressin (LVP). In the normal subjects, the addition of LVP potentiated the secretion of adenocorticotropic hormone (ACTH) induced by CRH, but had no significant effect on the secretion of other anterior pituitary hormones. In the combined test with 5 releasing hormones, the plasma ACTH and cortisol responses were not impaired in the majority of the patients before pituitary surgery. Serum thyroid-stimulating hormone (TSH), prolactin (PRL) and follicle-stimulating hormone (FSH) responses were not impaired in 82%, 70% and 67% of the patients, respectively, while the serum LH and GH responses were impaired in 67% and 73% of the patients, respectively. Following pituitary surgery, responses of these hormones to combined testing were similarly impaired in more than 75% of the patients. These results indicate that plasma ACTH, cortisol and serum TSH responses are fairly good before pituitary surgery but are impaired significantly after surgery. No subjects experienced any serious adverse effects related to the testing. These results suggest that combined testing with hypothalamic hormones is a convenient and useful method for evaluating pituitary function.
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BACKGROUND: Although most of pituitary apoplexy occur spontaneously, some precipitating factors have been reported. We experienced two cases of pituitary apoplexy after a pituitary function test. METHODS: In order to clarify the causal relation between the pituitary function test and apoplexy, we presented our two cases and reviewed 20 cases in the literature. RESULTS: (Case 1) A 48-year-old man with a pituitary macroadenoma received an injection of 500 micrograms thyrotropin-releasing hormone (TRH), 100 micrograms gonadotropin-releasing hormone (GnRH), and 0.1U/kg insulin as a preoperative test of pituitary function. Fifteen minutes later, he complained of diminished vision and headache. (Case 2) A 54-year-old man with a large cystic adenoma had an administration of 500 micrograms TRH and 100 micrograms GnRH. Ten minutes later, he complained of blurring of his left eye and headache. Although, in both cases, CT scans showed neither intratumoral hemorrhage nor infarction, the surgical specimen showed necrotic and hemorrhagic adenoma. The patients made excellent clinical recoveries after surgical decompression. Twenty-two reports including our two cases were reviewed. In 15 cases (68%), TRH was associated with apoplectic events and seemed to be the agent most likely to have an etiologic role because of its vasoactive properties. Eighteen patients (82%) had pituitary macroadenomas with suprasellar extension. In 72% of 18 surgical cases, some recovery of visual function was obtained. CONCLUSIONS: An apparent relationship between the test and the apoplectic events raises the possibility of the development of pituitary apoplexy after a pituitary function test. Unless there is a specific indication, pituitary function test should be avoided especially in patients with a large pituitary tumor.
In a prospective study of 26 patients with macroadenoma of the pituitary (14 secretory and 12 non-secretory), basal and stimulated pituitary hormone levels were used to detect hypothalamic dysfunction and to examine pituitary hormone secretion before and after hypophysectomy. Suprasellar tumour extention with hypothalamic compression occurred in 18 patients but was not consistently associated with hormonal tests indicative of hypothalamic dysfunction. In patients with secretory tumours, secretory activity was adequately assessed by basal hormone levels alone, which showed that surgery reduced hormone levels by a mean 85% in acromegaly and by a mean 55% in prolactinomas. Preoperatively, pituitary reserve of hormones not being hypersecreted was often normal, despite large tumour size and hypothalamic compression. Even after apparently complete pituitary removal at surgery, normal responses to stimulatory tests could sometimes be detected. Conventional dynamic tests are only of limited value in the assessment of hypothalamo-pituitary dysfunction in patients with large pituitary tumours and should not be used indiscriminately in such individuals requiring surgery.
Pituitary disorders can be diagnosed more readily and precisely as a result of two recent advances: development of radioimmunoassays for direct measurement of each pituitary hormone in blood, and availability of hypothalamic hormones for use in provocative tests for secretion of thyroid-stimulating hormone, prolactin, and gonadotropic hormones.
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.
Normal subjects were studied to test the feasibility of a combined anterior pituitary function test using iv administration of four hypothalamic releasing hormones: ovine corticotropin-releasing hormone, human GH-releasing hormone, GnRH, and TRH. Initially, nine normal men were studied with various combinations of these four hormones to exclude the possibility that they might inhibit or synergize with each other in releasing the individual anterior pituitary hormones. When given in combination, the releasing hormones were administered as sequential 20-sec iv infusions in the following order and doses: ovine corticotropin-releasing hormone, 1 microgram/kg; GnRH, 100 micrograms; human GH-releasing hormone, 1 microgram/kg; and TRH, 200 micrograms. Plasma or serum samples were assayed for ACTH, cortisol, GH, PRL, FSH, LH, and TSH at multiple times for 120 min after injection. Compared to individual administration, combined administration of these four hypothalamic releasing hormones caused no apparent inhibition or synergism with respect to the individual hormone responses of these normal subjects. Side-effects of the combined test were the same as those observed with individual hormone administration. No unusual or dangerous side-effects were observed. Having confirmed the efficacy of combined administration of the four releasing hormones, we administered the combination to five additional normal men and 12 normal women. Anterior pituitary hormone and cortisol responses were the same in men and women, except for a lower LH and a greater PRL response in women. There was a rapid increase in all hormones, with peak levels usually reached by 60 min. Adequate assessment of individual hormone responses can be achieved by assaying a basal and only 2 (or 3 in the case of ACTH and GH) postinfusion samples. A rapid, safe, and useful test of combined anterior pituitary function appears to be feasible using these four hypothalamic releasing hormones.
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Pituitary function was evaluated in a group of 10 patients with pseudocyesis. One patient was postmenopausal; the remainder demonstrated normal basal prolactin, luteinising hormone (LH) and follicle-stimulating hormone (FSH) levels and also normal pituitary-adrenal, pituitary-thyroid axes. Oestradiol deficiency was present in 6 patients, while 2 patients demonstrated elevated serum progesterone values, suggestive of a luteal phase. Gonadotrophin-releasing hormone administration resulted in exaggerated stimulation of LH and FSH in 4 and 2 patients, respectively. Impaired growth hormone (GH) secretion was present in 6 patients after insulin-induced hypoglycaemia and L-dopa administration. GH impairment is probably a consequence of the oestrogen deficiency that commonly occurs in this condition. It thus appears that there are aberrations in specific pituitary hormone responses after provocation in pseudocyesis.
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The hypophyseal gonadotrophin LH reserve was studied in 9 adult women, 5 of whom were suffering from nervous anorexia (N.A.) and 4 normal, by means of subcutaneous injection of 50 mcg of synthetic GN-RH. Basal values of plasmatic LH proved to be significantly lower in N.A. than in the controls where the response to GN-RH was prompt. In patients with N.A., on the other hand, response was practically absent and differences were significant at all stages of the test. The parallel study of basal steroiduria and following methopirone confirmed the torpid hypophyseal response in N.A. These findings confirm previous personal reports and indicate that the GN-RH test is a useful technique for diagnostic and prognostic definition of N.A.
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