[Hyperprolactinemia and sterility].
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Biomedical subjects
Publications and source records attributed to R Fahlbusch.
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The effect of bromocriptine withdrawal after long-term treatment on prolactin levels has been investigated in thirty-seven patients with prolactinomas. In ten patients with macroprolactinomas and post-operatively excessively high prolactin levels persisting suppression of prolactin secretion after bromocriptine withdrawal has been observed. This effect was not observed in patients with microprolactinomas or macroprolactinomas with only moderately elevated prolactin levels. The degree of persisting suppression correlated to the height of prolactin levels before treatment and to the duration of bromocriptine therapy. No correlation was found between the rise of prolactin levels after bromocriptine withdrawal and withdrawal time. It is suggested that the persisting suppression of prolactin levels is a sequence of reduction in tumour size. This anti-proliferative action of bromocriptine seems to be specific for the prolactin secreting cells in macroprolactinomas with high proliferation rate and high prolactin turn-over. These findings offer new possibilities in the management of patients with macroprolactinomas.
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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.
Hyperprolactinemia can be treated medically. Thus all patients with a normal sella turcica and those patients with only slight enlargement of the sella turcica can be treated medically with the dopaminagonist bromocriptine. This treatment is also indicated in paitents with postoperative persisting hyperprolactinemia. In contrast to hyperprolactinemia medical therapy of acromegaly is still in the experimental stage, through the dopaminagonist bromocriptine induces a decrease of growth hormone levels and improvement of the disease in many patients with acromegaly.
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Inappropriate stimulation of growth hormone (hGH)-secretion with TRH in acromegalic subjects has been shown previously, whereas prolactin (hPRL) secretion was reported to be blunted in active acromegaly. In this study TRH induced hGH and hPRL secretion was investigated in 23 active (mean hGH level: 68.5 +/- 19.9 ng/ml; +/- SE) and 15 inactive acromegalics (mean hGH level: 2.3 +/- 0.4 ng/ml; +/- SE). Fourteen of the active acromegalics showed a significant increase up to more than double of the basal hGH level after 200 mug TRH while in only one of the inactive acromegalics an inappropriate rise of hGH was induced by TRH. Basal hPRL levels were elevated in 9 and within normal range in 14 of the patients with active acromegaly. Except in 3 patients who had normal basal hPRL levels and in one patient with excessively elevated hPRL and hGH levels due to an hPRL and hGH producing adenoma, all patients had normal hPRL responses to TRH. In those with inactive acromegaly, 9 had hPRL levels below normal and only , out of the 15 patients showed a normal rise of hPRL after TRH. The patients who showed no hPRL response to TRH demonstrated also other signs of pituitary insufficiency due to the operative procedure. In contrast to a previous report these findings demonstrate that normal or enhanced hPRL secretion is found in active acromegaly. The inappropriate rise of hGH after TRH is compatible with a loss of specificity of the receptor for GRH of the adenoma cell and can be found also in patients with normal basal hGH levels after treatment suggesting that remaining adenoma tissue is present in the pituitary fossa.
A 22-year-old woman with recurrent goiter, hyperthyroidism, galactorrhea, and amenorrhea due to a pituitary tumor is described. She had been treated surgically twice for recurrent goiter with tracheal compression. Despite clinical signs of hyperthyroidism and slightly elevated plasma thyroid hormone levels (T4: 11 mug/dl; T3: 189 ng/dl), without thyroid hormone replacement therapy the basal TSH level was elevated up to 23 muU/ml and could not be suppressed by exogenous thyroid hormones: even when the serum thyroid hormone levels were raised into the thyrotoxic range (T4: 16.2 mug/dl T3: 392 ng/dl), the basal TSH fluctuated between 12 and 29 muU/ml. The basal PRL level was elevated up to 6000 muU/ml. The administration of TRH (200 mug iv) led only to small increments of TSH and PRL levels. Bromocriptin (5 mg p.o.) or l-dopa (0.5 g p.o.) suppressed TSH and PRL values significantly. After transsphenoidal hypophysectomy, TSH and PRL were below normal and the patient development panhypopituitarism. The adenoma showed two cell types which could be identified as lactotrophs and thyrotrophs by electronmicroscopy and immunofluorescence. From these data we conclude that the patient had a pituitary tumor with an overproduction of thyrotropin and prolactin.
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1. Hyperprolactinemia was found in 73 out of 445 patients as the underlying cause of primary or secondary amenorrhea, There was only in 65 cases both amenorrhea and galactorrhea. 2. Pituitary tumors were found in 21 cases. The causes of hyperprolactinemia in the other patients remained unclear. 3. Concentration of LH and FSH in serum was normal or lowered. Stimulation of LH and FSH by LHRH was possible only in part. 4. Regardless of the cause of hyperprolactinemia in all patients hPRL-levels were lowered significantly by 2.5 mg CB 154 within 4 hours. 5. Longtime suppression of hPRL by CB 154 normalized LH- and FSH- concentrations in serum and its response to LHRH. 6. Ovulatory cycles were observed in all cases treated by CB 154 (N = 25), 11 patients became pregnant.