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Evaluation of pituitary function in the fatigued patient: a review of 59 cases.
OBJECTIVE: The aim of this study was to review the results of dynamic pituitary testing in patients presenting with fatigue. METHODS: We reviewed clinical histories and insulin tolerance test (ITT) results of 59 patients who presented with fatigue and other symptoms of glucocorticoid insufficiency over a 4-year period. All patients referred for ITT had an early-morning cortisol level of <400 nM and a low or normal ACTH level. RESULTS: Peak cortisol and GH responses following insulin-induced hypoglycaemia were normal in only seven patients (12%). Median age of the remaining 52 patients was 47 years (range, 17-67 years); all but five were female. Common presenting symptoms were neuroglycopaenia (n = 47), depression (n = 37), arthralgia and myalgia (n = 28), weight gain (n = 25), weight loss (n = 9), postural dizziness (n = 15) and headaches (n = 13). Other medical history included autoimmune disease (n = 20; particularly Hashimoto's thyroiditis, Graves' disease and coeliac disease), postpartum (n = 8) and gastrointestinal (n = 2) haemorrhage and hyperprolactinaemia (n = 13). 31 subjects had peak cortisol levels of <500 nM (suggestive of ACTH deficiency; 18 of whom had levels < 400 nM) and a further six had indeterminate results (500-550 nM). The remaining 15 subjects had normal cortisol responses (median 654 nM; range, 553-1062 nM) but had low GH levels following hypoglycaemic stimulation (5.9 mU/l; 3-11.6 mU/l). CONCLUSION: Our results suggest that patients presenting with fatigue and symptoms suggestive of hypocortisolism should be considered for screening for secondary adrenal insufficiency, particularly in the presence of autoimmune disease or a history of postpartum or gastrointestinal haemorrhage. Whether physiological glucocorticoid replacement improves symptoms in this patient group is yet to be established.
The insulin hypoglycaemia test for the assessment of the hypothalamic--pituitary--adrenal function.
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Gonadotrophin-secreting pituitary tumour: report and review.
A 34-year-old male with a pituitary adenoma was investigated and demonstrated to have hypersecretion of both gonadotrophins in the basal state. Immunocytochemical staining and electron microscopic examination were positive for tumour cells secreting FSH and LH. Presenting symptoms included visual disturbances, loss of libido, impotence, cold intolerance, frontal headaches, change in skin pigmentation and excessive weight gain. The patient denied alteration in hair distribution, had no acral features, galactorrhoea or gynaecomastia. Surgical extirpation resulted in complete amelioration of his symptoms over a three year follow-up period. Basal and stimulated pituitary function testing results returned to normal post-operatively. A review of the literature documents six other cases of pituitary tumour secreting both LH and FSH in the basal state. More commonly, the pituitary adenoma secretes FSH only. The literature is reviewed with regard to both types of tumour.
Sheehan's syndrome of more than 30 years' duration: an endocrine and MRI study of 6 cases.
The endocrine function and pituitary imaging in Sheehan's syndrome more than 30 years after causative events were evaluated. Magnetic resonance imaging (MRI), a combined anterior pituitary test, plasma vasopressin-to-osmolality adaptation study, and antithyroid and antipituitary cell antibody measurement were performed in 6 women with Sheehan's syndrome. The interval from delivery to the onset of symptoms of hormonal deficiency ranged from 3 to 32 years. Since clinical onset, all had received glucocorticoid and thyroid replacement therapy. Cranial MRI examination showed an "empty sella" in 5 cases. Among these, 2 of 5 (40%) demonstrated panhypopituitarism and the other 3 (60%) maintained gonadotropin response. The pituitary gland was normally discernible but with a low-intensity lesion on T1-weighted images in a patient who maintained PRL and gonadotropin responses. Posterior pituitary function was abnormal in 3 of 6 (50%) despite the absence of polyuria. No antipituitary antibodies were detected in any of the cases. Thyroid peroxidase antibody was negative in all cases, but antithyroglobulin antibody was detected in 2 of 6 (33%). Thyroid-stimulating antibody was not detected, but one case had an anti-TSH antibody. Thirty years after the initial events, most patients with Sheehan's syndrome showed signs of an empty sella on MRI, all having noticeable suppression of anterior and/or posterior pituitary hormones with no related autoimmunity.
Transient diabetes insipidus and hypopituitarism after pituitary apoplexy: a rare association with pericardial effusion and painless thyroiditis.
Pituitary apoplexy in a 38-year-old male patient with acromegaly who presented with pericardial effusion, anterior pituitary dysfunction, and diabetes insipidus is described. With corticosteroid therapy, there was good initial recovery of pituitary function and regression of pericardial effusion. On withdrawal of corticosteroids, he developed painless thyroiditis, with transient thyrotoxicosis. Subsequently, the pituitary function tests remained normal for a year, but later he gradually developed hypogonadotropic hypogonadism, hypocortisolism, growth hormone deficiency, and progressive pituitary atrophy, resulting in empty sella syndrome.
[Pituitary thyrotropin and prolactin reserve in TRH stimulation test in pituitary dwarfism].
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[Insulin induced hypoglycemic test].
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[Water deprivation and water load test].
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[Pitressin test and DDAVP test].
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Assessment of pituitary function in patients with serum prolactin levels greater than 100 ng/ml.
Twelve women with galactorrhea-amenorrhea and prolactin levels greater than 100 ng/ml were evaluated with dynamic pituitary challenge testing. Forty-two per cent of the patients had positive findings on polytomography and subsequent surgical confirmation of a pituitary tumor. Patients with tumors had a delayed elevation of growth hormone (GH) and cortisol following induction of insulin hypoglycemia. Patients had increased thyroid-stimulating hormone levels after injection of thyrotropin-releasing factor, but showed blunting of prolactin secretion. Patients with tumors had decreased basal levels of GH and showed a blunted response to luteinizing hormone-releasing hormone (LRF) stimulation. These patients had normal elevations of follicle-stimulating hormone after LRF challenge. Patients with tumors showed a delay in elevation of GH levels following l-dopa treatment. They also failed to show prolactin suppression following this treatment. There are consistently predictive changes that occur in pituitary functions in the presence of a pituitary tumor. However, absolute prolactin levels and sellar polytomography are more reliable in diagnosing the presence of a pituitary tumor in the patient with galactorrhea-amenorrhea.
[Hypothalamic and pituitary function in brain death].
Hypothalamic and pituitary hormone levels were measured in 56 patients meeting the criteria of brain death proposed by the Japanese Ministry of Welfare. Pituitary hormone releasing tests were carried out in 39 patients. In addition, cerebral angiography and transcranial Doppler (TCD) were performed in 13 and six patients, respectively, just after hormone measurements. Serum hypothalamic and pituitary hormone levels were inconsistently high based on the half life time in the presumed absence of cerebral blood flow shown by angiography. The responses to releasing hormones were normal in 16 patients. TCD detected cerebral blood flow in the middle cerebral artery or ophthalmic artery in three patients who showed non-filling on angiography. Postmortem microscopic examination of the hypothalamus and anterior pituitary lobe revealed normal structure and cells intermingled with lytic changes and necrosis. This series suggests that some part of the hypothalamus and hypophysis may still be alive after brain death, although the function of these regions may be clinically insignificant.
A comparison between the 1-microg adrenocorticotropin (ACTH) test, the short ACTH (250 microg) test, and the insulin tolerance test in the assessment of hypothalamo-pituitary-adrenal axis immediately after pituitary surgery.
The short ACTH stimulation test is an easy, reliable, and extensively used test in the assessment of the hypothalamo-pituitary-adrenal (HPA) axis. However, its use immediately after pituitary surgery is a matter of debate. The insulin tolerance test (ITT) is the gold standard in the evaluation of the HPA axis, but it is not always without side effects and may be unpleasant early after pituitary surgery. Our aim was to investigate the value of the 1-microg ACTH test in the assessment of the HPA axis early after pituitary surgery. We also aimed to determine the value of the 1-microg and 250-microg ACTH tests and the ITT in the estimation of HPA axis status after 3 months postoperatively. Nineteen patients subjected to pituitary tumor surgery were included in the study, and the ITT and the 1-microg and 250-microg ACTH tests were performed between the 4th and 11th days of surgery. The tests were repeated at the first month in 3 patients with subnormal peak cortisol responses (454, 125, and 301 nmol/L) and in 18 patients at the third month postoperatively. ACTH stimulation tests were performed by using 1 microg and 250 microg ACTH iv as a bolus injection, and blood samples were drawn at 0, 30, and 60 min for measurement of serum cortisol levels. The ITT was performed by using iv regular insulin, and serum glucose and cortisol levels were measured. The 1-microg and 250-microg ACTH stimulation tests and the ITT were performed consecutively. At least 48 h were allowed between each test. A peak serum cortisol level of 550 nmol/L or greater was considered as a normal response for both the ITT and the ACTH tests. The serum cortisol level was measured by RIA using commercial kits. Serum glucose was determined by glucose oxidase method. There were correlations between the peak cortisol response to the ITT and the 1-microg ACTH test (r = 0.39, P < 0.05) in the early postoperative period. No correlation was found between the ITT and the 250-microg ACTH test responses. In the early postoperative period, two patients showed normal cortisol responses (> or =550 nmol/L) to the 1-microg ACTH test and five patients showed normal cortisol responses to the 250-microg ACTH test among the six patients with subnormal cortisol responses to the ITT. Three patients with subnormal cortisol responses to ITT and baseline cortisol values less than 240 nmol/L showed normal HPA axis at the end of the first month. In the late postoperative period, at the third month, all the patients showed normal HPA axis. In the early postoperative period of pituitary surgery, the 1-microg ACTH test results are more concordant than the 250-microg ACTH test in comparison with the ITT. Our results also indicate that HPA axis dysfunction shown by ACTH stimulation tests and the ITT in early postoperative period may be normalized 1-3 months after surgery. For this reason, we think that dynamic tests including the ITT may not be useful early after pituitary surgery.
Perphenazine-induced prolactin secretion in acromegaly.
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A combined anterior pituitary stimulation test: experience with 285 individuals.
A pituitary reserve test was performed in 285 individuals. Eighteen were healthy volunteers without any endocrine disease, 25 suffered from a presumed hypothalamic abnormality, 22 from hypopituitarism, 10 from acromegaly, 65 from the amenorrhea-galactorrhea syndrome, 2 from Nelson's syndrome, 32 from borderline primary hypothyroidism, 15 from borderline hyperthyroidism, 20 were on chronic levothyroxine therapy for primary hypothyroidism, and 15 had severe uncorrected primary hypothyroidism. Sixteen postmenopausal women were also included, as well as 15 patients with idiopathic ovarian failure and six with ovarian dysgenesis. Twelve male patients with hypergonadotropic and 12 with hypogonadotropic hypogonadism were also examined.The pituitary reserve test consisted of intravenous administration of a mixture of the thyrotropin-releasing hormone (TRH), gonadotropin-releasing hormone (GnRH), and regular insulin. The following tests were obtained prior to the injection only (time 0): serum thyroxine (T(4)), tri-iodothyronine (T(3)), T(3) resin uptake or thyroxine-binding globulin, total and free testosterone in men, estradiol and progesterone in women, and sex hormone binding globulin. At times 0, 20, 30, and 60 minutes, serum concentrations of the following compounds were obtained: glucose, adrenocorticotropic hormone, cortisol, growth hormone, prolactin, thyroid-stimulating hormone, luteinizing hormone, and follicle-stimulating hormone.Normal responses were established in a large number of cases. More or less typical patterns were demonstrated in the above-listed disease categories. Poor correlations between basal and stimulated values were observed, which emphasizes the diagnostic importance of the stimulation test. Maximum data were obtained using a combined test that has negligible morbidity, may be performed within an hour in an outpatient setting, and which examines the anterior pituitary function in a comprehensive fashion.
[Water-electrolyte regulating hormone and endocrinological tests].
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[Oral glucose loading test].
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Multiple ovarian cysts and oligomenorrhea as the initial manifestations of a gonadotropin-secreting pituitary macroadenoma.
OBJECTIVE: To report a case of a follicle-stimulating hormone (FSH)-secreting pituitary adenoma, which manifested with oligomenorrhea, dysmenorrhea, and multiple bilateral ovarian cysts. METHODS: We present a case report of a 29-year-old woman, including detailed laboratory, radiologic, and pathologic findings, who was diagnosed as having an FSH-secreting pituitary tumor. The pertinent literature is also reviewed. RESULTS: A 29-year-old woman, after experiencing oligomenorrhea and increasing abdominal girth for >1 year, presented with an acute abdomen. Ultrasonography revealed multicystic ovaries >15 cm in maximal diameter, causing bilateral adnexal torsion. After bilateral ovarian cystectomies, ultrasound study showed recurrence of the cysts. Relevant laboratory data were as follows: serum FSH 6.8 mIU/mL, luteinizing hormone 0.1 mIU/mL, prolactin 67 ng/mL, human chorionic gonadotropin <2 mIU/mL, progesterone 3.5 ng/dL, estradiol 237 pg/mL, thyrotropin 1.8 microIU/mL, testosterone <4 ng/dL, insulin 8.0 microIU/mL, and fasting plasma glucose 87 mg/dL. Magnetic resonance imaging (MRI) of the brain revealed a 2.5-cm pituitary mass, although the patient had no symptoms of pituitary dysfunction. Transsphenoidal removal of the mass was performed, and pathology studies were positive for FSH-secreting adenoma. Repeated MRI at 3 months showed an 0.8-cm residual tumor. The patient refused adjuvant radiotherapy. Regular menses resumed within 2 months postoperatively, and she later successfully became pregnant. Almost 3 years after treatment, the patient remained asymptomatic, results of pituitary function tests were normal, and follow-up MRI showed no signs of tumor regrowth. CONCLUSION: Although very uncommon, gonadotropin-secreting pituitary adenomas should be considered in the differential diagnosis of new-onset oligomenorrhea and dysmenorrhea, especially if associated with multicystic ovaries on ultrasound study, even in the absence of elevated levels of serum gonadotropins. Furthermore, we propose that it may be acceptable to withhold adjuvant radiotherapy in patients who are asymptomatic after transsphenoidal surgical excision of these tumors.