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The TSH response to thyrotropin-releasing hormone (TRH) in young adult men: intra-individual variation and relation to basal serum TSH and thyroid hormones.

The response of serum TSH to duplicate tests with each of two doses of TRH (30 mug and 500 mug) was studied in 22 normal young adult men. The mean intra-individual variability of the response assessed by duplicate testing (coefficient of variation) was 17% but was as high as 63% in individual subjects. While the actual range of peak TSH values after 500 mug TRH was 2.7-19.5 muU/ml, those subjects (3 of 22) with a peak TSH value between 2 and 5 muU/ml on one occasion were all greater than 5 muU/ml on another. Thus, despite the intra-individual variability, a peak TSH value after 500 mug TRH of less than 2 muU/ml indicates TSH deficiency and greater than 5 muU/ml indicates normal TSH reserve. A peak value of 2-5 muU/ml is an indication for retesting;; a peak TSH value greater than 5 muU/ml on retesting indicates normal TSH reserve. The use of the maximal increase in TSH above basal values (max deltaTSH) did not have a clear advantage over the use of the peak TSH value although a max deltaTSH greater than 4 muU/ml was equivalent to a peak value greater than 5 muU/ml. No information was lost by using only the TSH value at 30 min after TRH instead of multiple samples. In using these values differences in assay technique should be considered; for example, the use of human TSH standard MRC 68/38 instead of human TSH standard A (MRC 63/14) causes a fall of about 1/3 in measured serum values. The overall TSH response to 500 mug TRH was statistically greater than the response to 30 mug TRH (P less than 0.01); however, in 10 of 22 subjects the response to the two doses was about the same, suggesting that the dose response of TSH to TRH, between 30 mug and 500 mug TRH, is quite shallow. The TSH value 60 min after 500 mug TRH was within 2 muU/ml of the peak TSH value in 12 of 22 subjects on at least one occasion; this pattern of a delayed fall is a normal variant. The peak TSH response to TRH correlated well with the basal level of TSH (P less than 0.001) and thus can be considered a magnifier of the basal level of TSH in normal subjects. While the peak TSH value did not correlate with the basal level of T3, there was a moderate negative correlation of the peak TSH value with the basal level of T4 (P less than 0.02), suggesting that the concentration of serum T4 within the normal range is a determinant of TSH secretion.

Adolescent↗

Pituitary apoplexy. A review.

Pituitary apoplexy, a rare but life-threatening condition, may be highly variable in its clinical appearance and therefore should be considered in any patient with abrupt neurologic deterioration. We reviewed the literature on acute massive pituitary infarction to create an awareness of predisposing factors, the pathophysiologic mechanisms responsible for its heterogeneous manifestations, and possible options for investigation and management. These concepts are reinforced by examining the course and outcome of a rare case of pituitary apoplexy manifesting a full range of neurologic and endocrine abnormalities.

Adenoma↗

Gamma knife radiosurgery for pituitary adenomas: usefulness of combined transsphenoidal and gamma knife radiosurgery for adenomas invading the cavernous sinus.

Thirty-seven of 317 patients with pituitary adenoma who underwent transsphenoidal operation from 1989 to 1996 received adjuvant gamma knife radiosurgery. Gamma knife surgery was performed mainly in patients with endocrinologically inactive tumor for tumor regrowth invading the cavernous sinus, and in patients with endocrinologically active tumor for incomplete removal invading the cavernous sinus. The maximum radiation dose was 25-60 Gy. The periphery of the tumor usually received 50% of the maximum dose. Thirteen patients were followed up for longer than 2 years (mean 45 months) after combined therapy. Magnetic resonance imaging (MRI) showed changes in signal intensity on both T1- and T2-weighted images as early as 3 months after radiotherapy. Serial MRI showed all 13 patients had achieved excellent response. Patients with endocrinologically active tumors showed normalized hormone levels 24 months after gamma knife surgery except for one patient with acromegaly. The basal value of pituitary hormones remained normal during the follow-up period, and four female patients became pregnant without hormonal therapy. Combined transsphenoidal surgery and gamma knife radiosurgery can preserve normal pituitary function and eradicate adenoma invading the cavernous sinus.

Adenoma↗

A comparative trial of transsphenoidal hypophysectomy and estrogen suppression with aminoglutethimide in advanced breast cancer.

We compared two treatment regimens, transsphenoidal hypophysectomy and estrogen suppression with aminoglutethimide in women with metastatic breast carcinoma. Three of fourteen patients experienced partial objective tumor regression with a median duration of 4.6 months following hypophysectomy, whereas 10 of 21 women receiving aminoglutethimide responded (2 complete, 8 partial) with a median duration of 11.5 months. Side effects in the medical group were minimal while surgical complications included 2 cases of CSF rhinorrhea, one leading to meningitis and death. In patients receiving aminoglutethimide, urinary free cortisol and plasma dehydroepiandrosterone sulfate fell significantly as did plasma estrone and estradiol. In the hypophysectomy group, anterior-pituitary function testing postoperatively revealed adequate suppression of gonadotropin and prolactin secretion but incomplete inhibition of the ACTH-cortisol axis in 4 of 7 surgical patients studied. Five patients initially treated with hypophysectomy experienced a further reduction of plasma (and urinary) estrone and estradiol levels when given aminoglutethimide. We conclude that estrogen suppression therapy with aminoglutethimide is a feasible alternative to surgical hypophysectomy in providing endocrine suppression and palliation in advanced breast carcinoma.

Adult↗

Effect of combination chemotherapy on pituitary-gonadal function in patients with lymphoma and leukemia.

After at least four courses of intermittent chemotherapy, 14 of the 15 men with malignant lymphoma had elevated serum follicle-stimulating hormone (FSH). In three of these subjects, serial studies showed progressive increases in basal FSH and exaggerated FSH responses to luteinizing hormone releasing hormone (LHRH). Although gonadal biopsies were not done, this elevation of FSH is indicative of progressive and severe damage to the germinal epithelium by chemotherapy. Elevated leutinizing hormone (LH) was found in seven and decreased testosterone (T) in two of these subjects. Increased LH responses to LHRH stimulation were also found in the three subjects studied. These findings suggest that the testicular damage is not restricted to the germinal tissue. In four male subjects with acute myeloid leukemia treated by intermittent chemotherapy not containing any alkylating agents, FSH, LH, and T levels were normal. Three of the 4 female patients with malignant lymphoma and two with acute myeloid leukemia had normal basal, serial, and LHRH-stimulated FSH, LH, and estradiol (E2) levels. Elevated gonadotropins and low E2 were found only in subjects who had received abdominal irradiation.

Adult↗

Hypophysitis in surgical and autoptical specimens.

We present the clinical and histological findings of 11 cases of inflammatory anterior pituitary lesions, 8 of which were obtained during surgery and 3 of which were obtained from autopsies. Additionally, we extended the conventional classification of pituitary inflammatory disease by the new entity " secondary hypophysitis". Of the surgically obtained specimens 5 consisted of inflammatory extension into the pituitary gland out of the surrounding tissue. In all of these patients the inflammation originated from an additional tumor in the sellar region (4 craniopharyngiomas, 1 prolactinoma). These will be referred to as "secondary hypophysitis", an entity which has not yet been mentioned in the literature. Of the remaining 6 cases, 2 were granulomatous hypophysitis, 2 pituitary abscesses, 1 lymphocytic hypophysitis, and 1 showed extensive scarring of the anterior pituitary lobe due to preceeding lymphocytic hypophysitis. At histological examination the basic structure of the anterior pituitary was maintained in all cases. Relative counts of hormone-producing cells were normal. In secondary hypophysitis, the affected area was composed of fibrous tissue and granulation tissue. B and T lymphocytes were present in equal amounts. Granulomas were not found. Inflammatory infiltrates, granulation tissue and fibroses were seen in different proportions. Based on our results and three other cases reported in the literature so far, we think that the presently used classification of pituitary inflammatory diseases lacks an entity which describes a non-abscess-forming inflammation of the pituitary gland originating from an associated pathological process. Therefore, we introduced the term secondary hypophysitis to describe this fourth entity of pituitary inflammatory disease.

Adult↗

Metastases to the pituitary--hypothalamic axis. An MR study of 7 symptomatic patients.

Seven patients with metastatic tumour in the pituitary-hypothalamic axis were investigated by MRI. The main clinical problems were diabetes insipidus (5 cases) and general pituitary dysfunction (2 cases). No patient had visual or oculomotor symptoms. In 6 of the 7 patients the primary malignant tumour was known, but no patient had symptoms from the primary tumour; 1 had symptoms from metastases in locations other than the pituitary gland. In one patient no primary tumour was known. MR detection of a second, clinically silent, 5 mm lesion in the posterior cranial fossa initiated the search for primary tumour. MRI showed purely suprasellar tumours in 3 patients and intra- and suprasellar tumours in 4. The latter were dumbbell lesions with only a small bridge of tissue connecting the intra- und suprasellar portions. Six of the 7 suprasellar tumours seemed to be in the infundibular recess of the third ventricle; in 5 the infundibulum was visible as an enhancing linear structure at the postero-inferior border of the tumour. The pituitary fossa was normal in all cases.

Adult↗

Review of the embryologic development of the pituitary gland and report of a case of hypophyseal duplication detected by MRI.

We describe the clinical manifestations, associated abnormalities, MRI appearances and pathologic significance of a case of hypophyseal duplication. A 16-year-old girl presented with delayed sexual development and history of midline craniofacial anomalies. MRI revealed paired infundibula extending inferiorly to two small pituitary glands, a midline hypothalamic mass, and a midline cleft in the basisphenoid. Twelve cases of pituitary duplication have previously been described. The suggested pathogenesis is duplication of the prechordal plate and anterior end of the notochord during early embryologic development.

Abnormalities, Drug-Induced↗

Suprasellar germinomas; relationship between tumour size and diabetes insipidus.

The clinical and neuro-endocrinological aspects of 17 suprasellar germinoma patients treated between 1972-1991 are reported. Surgical extirpation was not initially attempted, but all patients received irradiation with or without a biopsy. Sixteen of those have led useful lives with appropriate hormonal replacement therapy during a mean follow up of 8 years. Seven tumours at diagnosis were less than 2 cm in diameter (type 1), nine tumours more than 2 cm (type 2), and one double midline tumour was of unknown size. All 7 type 1 patients required 1-deamino-8-D-arginine-vasopressin (DDAVP) to control diabetes insipidus (DI), but only 2 of the 9 type 2 patients have needed DDAVP since completion of the treatment. Patients with smaller tumours required more DDAVP following tumour disappearance, than those with larger tumours. The prognostic indicators for the post-treatment course of DI and retarded growth appeared to be the tumour size and the age at diagnosis. We also emphasize the absence of metastasis in unoperated cases and the use of tumour markers as a diagnostic criterion which obviates surgical acquisition of tissue to make the diagnosis. Possible reasons are discussed and the literature reviewed.

Adolescent↗

Treatment of craniopharyngiomas--the stereotactic approach in a ten to twenty-three years' perspective. II. Psychosocial situation and pituitary function.

Fourty-two consecutive patients with craniopharyngioma were treated by "stereotactic approach", i.e. preferentially stereotactic puncture and installation of colloid isotope into cystic tumours and external stereotactic single dose irradiation to solid tumour parts. In a minority of cases, such treatment was less suitable, and surgical removal and/or radiotherapy was used. There was no peroperative mortality. A long-term follow up (observation time 10-23 years) of the 31 patients alive indicated that they were socially well adapted with a high rate of fulltime work and a low rate of intercurrent disease. In spite of substitution therapy for pituitary insufficiency in most cases, the patients were subjectively seldom disturbed by their disease. Our results support a change in the choice of therapy for craniopharyngioma patients, from open neurosurgery to the less invasive stereotactic techniques.

Adolescent↗

Characteristics of giant pituitary adenomas.

An analysis of 21 giant pituitary adenomas is presented. Giant pituitary adenomas with a diameter of more than four cm mostly perforate dura and diaphragm, invade the cavernous sinus, and spread extradurally into anterior and middle cranial fossae or into the frontal or temporal lobes. Endocrinologically, a third are prolactinomas, and a half are non-secreting tumours leading to pituitary failure. Clinical, radiological, and operative characteristics lead to the conclusions that multishaped dura-penetrating extension is not due to locally destructive growth, but is the result of late diagnosis. Because radical cure by operation and radiotherapy is hardly likely, early operative treatment is necessary even when an excellent endocrinological response to medical therapy is present.

Adenoma, Chromophobe↗

[Increased prevalence of osteoporosis and arteriosclerosis in conventionally substituted anterior pituitary insufficiency: need for additional growth hormone substitution?].

In a retrospective study of 632 patients with pituitary disease we diagnosed pituitary insufficiency without hypersecretion of any pituitary hormone in 122 patients. Patients were substituted with sex hormones (76%), hydrocortisone (74%) and/or L-thyroxine (77%). 76% had additional growth hormone deficiency, as shown by an increase of growth hormone of less than 5 ng/ml after i.v. administration of L-arginine. In 17% of all patients the diagnosis of osteoporosis was proven or suspected radiologically. 57% had low bone mass of lumbar spine (dualphotonabsorptiometry) and 73% had low bone mass of the proximal forearm (singlephotonabsorptiometry). BMD values of pituitary insufficient patients were in the same range as those of patients with established osteoporosis. More than half of all patients (53%) complained of tiredness, exhaustion and muscle weakness. 40% suffered from adipositas. 77% had hyperlipidemia (68% hypertriglyceridemia and 42% hypercholesterinemia), 18% had hypertension. 14% of the patients had arteriosclerotic events in their history (myocardial infarction or stroke). These figures are higher than incidences shown in the German PROCAM-study. These data show an increased prevalence of osteoporosis and vascular diseases. This is in contrast to the general opinion, that patients with pituitary insufficiency are adequately treated by substitution with adrenal, thyroid and sex hormones. Whether other factors such as the additional growth hormone deficiency are responsible for these diseases has to be examined in prospective studies.

Adolescent↗

Pituitary granuloma and chronic inflammation of hypophysis: clinical and immunohistochemical studies.

We describe five patients with chronic inflammation of the hypophysis including three pituitary granulomas of unknown aetiology. In contrast to the previously reported cases, the involvement of neurohypophysis or hypothalamus was a distinct clinical feature in these patients. Impairment of anterior pituitary function was less prominent, while polyuria and polydipsia occurred in all cases. Enlargement of the sella turcica was absent in three and slight in two cases. CT scan and MR images demonstrated a contrast-enhanced sellar mass in all patients; abnormally thickened pituitary stalk and infundibulum with contrast-enhancement was observed in four. The fibrous tissues were removed by the transsphenoidal approach in four patients, and by the subfrontal approach in one case. In all patients, the endocrinological dysfunction was prolonged. No increase in the size of the remaining pituitary mass was demonstrated on repeated MR images in any of the patients. On histological examination, granulomatous formation was present in three samples, and multinucleated Langhans' giant cells were seen in one. The epithelioid cells and multinucleated giant cells constituting the granulomas were positive for anti-macrophage antibody. No firm laboratory or histological evidence was obtained supporting the presence of systemic disease leading to granulomas. In the other two cases, the pituitary lesions were composed of chronic inflammation tissue, and serum antipituitary antibodies were present in a patient with concurrent Hashimoto's thyroiditis. Our experiences with chronic inflammation of the hypophysis indicate that these patients are best managed by histological confirmation of the lesion followed by adequate hormonal replacement.(ABSTRACT TRUNCATED AT 250 WORDS)

Corticosterone↗

Treatment of patients with prolactinomas.

Fifty-one female patients with prolactin producing tumors (PRL 1100 to 88,000 microU/ml) and 26 male patients with prolactin producing tumors (PRL 6500 to 400,000 microU/ml) were studied. Only 25% of the females had visual field defects which were present in 70% of the males. All females had amenorrhea but only 35 had galactorrhea. Hypopituitarism was rarely seen in the females but in most of the male patients. Twenty-four females and all male patients were operated (transphenoidal or transfrontal operation). PRL normalized in only eight females and in none of the males. Two patients became pregnant postoperatively, four after postoperative treatment with bromocriptine. Bromocriptine induced regular menses in 4 other patients operated by transsphenoidal route. Eight patients with microadenoma (PRL less than 4000 microU/ml) were treated with bromocriptine alone of whom two became pregnant. The males were also treated with bromocriptine leading to a significant fall of the PRL level accompanied by improvement of libido, sexual potency and headache. Two patients received radiation postoperatively, which led to a fall of PRL and improvement of visual fields. Since PRL levels remained low after withdrawal of bromocriptine for several months an antiproliferative effect of this drug is suggested. Thus differential therapy of PRL producing tumors is possible: In females selective neurosurgery can alone or combined with medical therapy normalize PRL secretion and ovarian function. In patients with microadenoma bromocriptine alone can be successful. In patients with inoperable large tumors radiation should be advocated. Additional bromocriptine therapy may be helpful to stop tumor growth and alleviate the effects of hyperprolactinemia.

Adenoma↗