Discordant patterns of hyperprolactinaemia and galactorrhoea in secondary amenorrhoea

There were 123 patients with functional secondary amenorrhea of at least 6 months' duration. The upper normal serum prolactin level was 3 ng/ml as measured by radioimmunoassay. Hyperprolactinemia was found in 40 of the 123 patients (33%). Those with peak levels of 60 ng/ml often also had some normal levels. Patients with levels over 120 had demonstrable galactorrhea in 38% of cases. Galactorrhea was found in 10 patients with normal prolactin values. The 5 patients with anorexia nervosa had normal prolactin values and no galactorrhea. 14 of 61 (23%) patients with self-induced weight loss had hyperprolactinemia but galactorrhea was rare. Hyperprolactinemia was found in 4 of 13 patients with stress-related amenorrhea. Amenorrhea after use of oral contraceptives was related to hyperprolactinemia in 10 of 28 patients and 5 had galactorrhea. There were 4 patients with the Chiari-Frommel syndrome; their mean serum prolactin level was 435 ng/ml. 5 patients had pituitary tumors; galactorrhea was present in 3 of them. All of these 5 patients had high serum prolactin levels ranging from 145 to 620 ng/ml. Mild hyperprolactinemia was present in 16 patients with idiopathic amenorrhea but no galactorrhea. 5 of the 9 patients who were hirsute had elevated prolactin. Results show that galactorrhea is not a reliable sign of hyperprolactinemia. The prolactin assay is helpful in the management of patients with amenorrhea.     

Acromegaly and galactorrhea-amenorrhea with two pituitary adenomas secreting growth hormone or prolactin. A case report

A prolactinoma was removed from a nulliparous woman who had acromegaly, galactorrhea-amenorrhea, elevated serum growth hormone and prolactin, and hypogonadotropinism. Postoperatively galactorrhea decreased and cyclic vaginal bleeding ensued; serum prolactin concentration was normal but growth hormone remained elevated and the acromegalic complex was unchanged, even after subsequently administered bromocriptine. At a second transsphenoidal operation, an adenoma of somatotropes was removed; improvement in symptoms and signs and normalisation of pituitary function, including growth hormone, followed. The possible presence of distinctly separate pituitary adenomas should be considered in patients with galactorrhea associated with acromegaly.     

Estrogen-induced galactorrhea in man

A 36-year-old man had estrogen-induced galactorrhea and oligospermia. He had been taking an unknown amount of estrogen for a year. While hypogonadism, manifested by decreased libido and potency, was apparent at the time of estrogen administration, galactorrhea appeared two months after estrogen was discontinued. Normal skull film, tomogram views of the sella turcica, and computerized axial tomography scan suggested that long-term estrogen administration caused sustained hyperprolactinemia with levels that ranged between 21 and 83 ng/mL throughout the ensuing year. Prolonged thyroid-stimulating hormone and prolactin luteinizing hormone response to luteinizing hormone-releasing hormone were believed to be evidence of a derangement in the hypothalamic control of pituitary hormone secretion. A year after he stopped taking estrogen, the patient gradually regained his potency, his prolactin level declined, the galactorrhea disappeared, and spermatogenesis returned to normal.     

Hypoglycemia-induced prolactin release

Recent advances in neurosurgical techniques have made it possible to remove pituitary adenomata with minimal morbidity and mortality. These developments have focused attention on early recognition of pituitary tumors, before the onset of visual disturbances or endocrine dysfunction. We have studied the prolactin response to insulin-induced hypoglycemia as an aid in the evaluation of patients with hypothalamic and pituitary disease. Regular insulin 0.1 units/kg was administered intravenously to normal subjects, to patients with pituitary tumors, and to patients with idiopathic galactorrhea. While the normal subjects regularly showed a prolactin response to hypoglycemia, this was observed infrequently in the other groups. It is possible that prolactin nonresponsiveness to insulin hypoglycemia may reflect nonspecific pituitary damage or may represent an abnormality specific to patients with galactorrhea. Our data suggest that the prolactin response to insulin hypoglycemia is a sensitive index of hypothalamic-pituitary dysfunction.     

Characterization of a pituitary stone

Calcification of the pituitary is unusual and functional studies of such cases have not been previously reported. We have been able to document persistent prolactin secretion both in vivo and in vitro in a patient with a severely calcified pituitary adenoma (“pituitary stone”), and have also documented prolactin granules within the calcified tissue mass. Normal menstrual function was restored after surgical removal of the “stone,” and galactorrhea subsided although the prolactin response to thyrotropin-releasing hormone (TRH) remained abnormal. Two years after surgery the menstrual cycle has remained regular, but galactorrhea has recurred, emphasizing the need for prolonged follow-up in patients with prolactin-producing adenomas, despite apparent surgical cure. The in vitro studies showed that human pituitary tissue is secretory in culture and thus may serve as a useful tool for physiologic studies of the pituitary cell.     

Be careful …. She has a pituitary gland in her nose

In this case report we describe a 38 year-old-female with galactorrhea several months after the birth of an anencephalic child. She had hyperpolactemia and imaging of the pituitary gland revealed a midline defect and a nasopharyngeal mass compatible with a meningo-(hypophyso-) encephalocele and possibly an ectopic teratoma or desmoid. She was treated with dopamine agonists for 10?years and after cessation of therapy her prolactin levels remain normal. The nasopharyngeal mass remained unchanged over time and there were no signs of hypopituitarism. The hyperprolactinemia at presentation was probably caused by earlier pregnancy and stalk dysfunction due to traction by the mass. With decline of pituitary size, after starting dopamine agonists, the traction probably reduced resulting in a normal prolactin level. Our patient was warned against manipulation in de nose, because this could damage the meningo-encephalocele. An MRI will be preformed every 2?years to monitor changes in de mass.     

Be careful …. She has a pituitary gland in her nose

In this case report we describe a 38 year-old-female with galactorrhea several months after the birth of an anencephalic child. She had hyperpolactemia and imaging of the pituitary gland revealed a midline defect and a nasopharyngeal mass compatible with a meningo-(hypophyso-) encephalocele and possibly an ectopic teratoma or desmoid. She was treated with dopamine agonists for 10 years and after cessation of therapy her prolactin levels remain normal. The nasopharyngeal mass remained unchanged over time and there were no signs of hypopituitarism. The hyperprolactinemia at presentation was probably caused by earlier pregnancy and stalk dysfunction due to traction by the mass. With decline of pituitary size, after starting dopamine agonists, the traction probably reduced resulting in a normal prolactin level. Our patient was warned against manipulation in de nose, because this could damage the meningo-encephalocele. An MRI will be preformed every 2 years to monitor changes in de mass.

     

Be careful …. She has a pituitary gland in her nose

In this case report we describe a 38 year-old-female with galactorrhea several months after the birth of an anencephalic child. She had hyperpolactemia and imaging of the pituitary gland revealed a midline defect and a nasopharyngeal mass compatible with a meningo-(hypophyso-) encephalocele and possibly an ectopic teratoma or desmoid. She was treated with dopamine agonists for 10 years and after cessation of therapy her prolactin levels remain normal. The nasopharyngeal mass remained unchanged over time and there were no signs of hypopituitarism. The hyperprolactinemia at presentation was probably caused by earlier pregnancy and stalk dysfunction due to traction by the mass. With decline of pituitary size, after starting dopamine agonists, the traction probably reduced resulting in a normal prolactin level. Our patient was warned against manipulation in de nose, because this could damage the meningo-encephalocele. An MRI will be preformed every 2 years to monitor changes in de mass.     

RESOLUTION OF ACROMEGALY AFTER REMOVAL OF A BRONCHIAL CARCINOID SHOWN TO SECRETE GROWTH HORMONE RELEASING FACTOR

A 29 year old woman with an enlarged pituitary fossa and classical acromegaly, possibly present for ten years, had biochemical and partial somatic resolution of the disorder after removal of a bronchial carcinoid tumour. In addition, galactorrhea stopped, menstruation returned after two years, and amenorrhea and elevated prolactin levels fell towards normal.
Immunocytochemistry showed numerous growth hormone releasing factor (GRF) staining cells in the tumour. The tumour cells, when cultured, produced a supernatant selectivity stimulating human pituitary somatotrophic cell cultures to produce growth hormone (GH). The bronchial carcinoid did not secrete detectable GH, but extracts of it, and preoperative serum contained GRF immunoreactivity which coeluted with synthetic human pancreatic GRF.     

Primary empty sella, galactorrhea, hyperprolactinemia and renal tubular acidosis.

Discussed here is a 41 year old woman with galactorrhea associated with the empty sella syndrome and mild renal tubular acidosis. Basal serum prolactin (PRL) levels were normal, but a 24 hour serum PRL secretory profile demonstrated an increased mean PRL concentration. Serum PRL was appropriately suppressed by the administration of L-dopa; however, chlorpromazine stimulation resulted in a blunted serum PRL response. Pituitary luteinizing hormone, follicle stimulating hormone, ACTH and thyroid stimulating hormone levels were normal. Thus, galactorrhea associated with an enlarged sella does not establish the diagnosis of a pituitary tumor, and pneumoencephalography must be performed to exclude the empty sella syndrome.     

Primary hypothyroidism mimicking pituitary macroadenoma

A 21-year-old woman complaining of 8-month amenorrhea associated to weight gain, galactorrhea and frequent headaches, presented for clinical evaluation; her laboratory tests were: TSH: 1192 mUI/ml (0.27-4.2); TT4: 1.0 microg/dl (4.4-11.4 l); TT3: 0.41 ng/ml (0.7-2.1); prolactin: 69.2 ng/ml (3-20) and a diagnosis of myxedema associated to galactorrhea was made. A hypothalamic-pituitary magnetic resonance imaging (MRI) showed a suprasellar and intrasellar mass lesion of 1.9 x 1.4 x 1.9 cm, determining compression and deviation of the optic chiasm. Due to the possibility of hyperplasia of the TSH-producing cells, treatment of hypothyroidism was initiated with levothyroxine. Two months later, upon normalization of thyroid hormones and TSH levels, a second MRI showed an anatomically normal pituitary gland. Regression of the pituitary mass after treatment with levothyroxine confirmed the hypothesis of pituitary hyperplasia secondary to primary hypothyroidism. Our findings support the importance of determining thyroid function tests during the investigation of pituitary masses and thus avoiding an unnecessary surgery.     

The effect of metoclopramide, TRH and L-dopa on prolactin secretion in pituitary adenoma and in "functional" galactorrhoea syndrome.

The degree of autonomy in prolactin secreting pituitary adenomas and also prolactin secretory reserve in cases with suspected functional galactorrhea syndrome was evaluated with the use of metoclopramide, TRH and L-DOPA. It was found that in patients with pituitary adenoma the basal prolactin (PRL) level often exceeded 150 micrograms/l and the response to stimulation with TRH and/or metoclopramide was markedly diminished or even nonexistent, while the response to L-DOPA was usually retained. In patients with galactorrhoea and/or amenorrhoea, with normal skull X-ray the basal PRL level was either normal or moderately raised but the response to stimulation was various; mostly it was excessive, it was sometimes normal, but in some other cases it was markedly diminished as in patients with adenoma. In the author's opinion the so-called "functional disorder" of prolactin secretion is mainly hyperresponsiveness to stimulation, whereas the basal PRL level in those cases is usually normal or only intermittently raised. In the cases with a moderate hyperprolactinaemia, especially if it appears to be constant, and the response to stimulation is diminished or none at all, we suspect a pituitary microadenoma. Finally, there are rare cases of galactorrhoea with normal basal PRL and normal response to stimulation, in which the sensitivity of the mammary PRL receptor is probably increased. We suggest therefore that the above mentioned PRL stimulation tests may help in distinguishing between tumoural and functional hyperprolactinaemia.     

Patients with primary hypothyroidism presnting as prolactinomas

Hyperprolactinemia can occur in patients with primary hypothyroldism. Two women with hypothyroidism who had elevated serum prolactin levels, galactorrhea, amenorrhea, and pituitary computed tomographic scans that demonstrated the presence of “pituirary tumors” were recently evaluated. It was believed that they had prolactinomas, and they were referred for possible surgery. An elevated serum thyroid-stimulating hormone level, however, suggested that they had primary hypothyroidism and probably pituitary enlargement secondary to pituitary hyperplasia. Detailed evaluation of thyroid-stimulating hormone and prolactin secretion was performed. These studies revealed several abnormalities in dopamine-prolactin interactions; however, the primary event responsible for the hyperprolactinemia is unclear. These women were given thyroxine therapy, and subsequent radiologic and endocrine studies documented resolution of their “pseudotumors” and normalization of the serum thyroxine and prolactin levels. Hence, thyroid-stimulating hormone levels should be measured in all patients presenting with a suspected prolactinoma so that any hypothyroidism that is noted is not presumed to be due to secondary hypothyroidism from tumor involvement of the pituitary.     

Prolactin regulation in 14 cases of galactorrhea and hypogonadism with minimal modifications of the sella turcica (author's transl)]

In this study we report 13 cases of amenorrhea-galactorrhea and one of a male patient complaining of gynecomastia, galactorrhea, sexual impotence and sterility with oligoasthénospermy. In these cases, the size of the sella turcica was normal but we found a localized depression of the bottom of the sella turcica; these modifications were situated at the antero-inferior part of the sella in 12 cases and posteriorly in the 2 others. Basal prolactin level was higher than normal values in 13 cases (12 female and 1 male patients): individual values varied between 45 and 367 ng/ml. Nycthermeral rhythm disappeared in the 9 cases studied. Administration of L-Dopa (500 mg orally) significantly suppressed the prolactin values in the 11 cases studied. Oral water loading (20 ml/kg) left prolactin values unchanged (10 cases). After oral glucose tolerance test (1 g/kg) no significant systematic variation occurred. The increase of prolactin values after stimulation by 200 microg. TRH IV as a bolus (4 cases) was not significant. We have found similar prolactin variations in cases of hyperprolactinemia with either normal pituitary fossa (7 cases) or macro-adenoma (6 cases).     

Inhibition of thyrotropin and prolactin secretion by dopamine in man

The effect of dopamine on thyrotropin (TSH) and prolactin (PRL) levels was studied in 5 normal subjects, 7 women with galactorrhea, 9 acromegalics and 4 patients with primary hypothyroidism. Dopamine infused at the rate of 280 micrograms/min produced significant decrease in plasma TSH and PRL levels in all four groups, though a lower fall in TSH was noted in acromegalics. A similar reduction in PRL was also noted after 28 micrograms/min dopamine. Phentolamine infusion (0.5 mg/min) had no effect on PRL response to dopamine. These results indicate that a dopaminergic stimulation led to an inhibition of TSH and PRL secretion. Since the high polarity of dopamine impedes its passage through the blood-brain barrier, its site of action should be outside this barrier, probably in the pituitary.     

Prevalence of pituitary adenomas in macroprolactinemic patients may be higher than it is presumed

One form of prolactin (PRL) is macroprolactin with high molecular mass. Many macroprolactinemic patients have no pituitary adenomas and no clinical symptoms of hyperprolactinemia, it is controversial whether macroprolactinemia is a benign condition that does not need further investigation and treatment. In this study, we aimed to compare macroprolactinemic patients (group I) with the true hyperprolactinemic patients (group II) for the presence of pituitary adenoma. We investigated 161 patients with hyperprolactinemia, whose magnetic resonance imaging records of the pituitary were taken. All patients were questioned for irregular menses, infertility and examined for galactorrhea. Patients were screened for macroprolactinemia by polyethylene glycol precipitation, and a recovery of ≤40% and normal monomeric PRL level was taken as an indication of significant macroprolactinemia. Of 161 patients with hyperprolactinemia, 60 (37.26%) had macroprolactinemia. PRL levels of group II were lower than those of group I (P = 0.011), although monomeric PRL levels of group II were higher than those of group I (P = 0.0005). Of 60 macroprolactinemic patients, 16 (26.7%) had pituitary adenomas. The prevalence of pituitary adenomas was lower in group I, compared with group II (P = 0.0005). No significant differences were found between the prevalences of irregular menses and infertility of group I and II (P = 0.084, P = 0.361). Prevalence of galactorrhea in group I was lower than that in group II (P = 0.048). Prevalence of pituitary adenomas in macroprolactinemic patients is lower compared with the true hyperprolactinemic patients, but may be higher than that found in other recent studies and in the general population.     

Pituitary tuberculosis: a case report

Through a case of sellar and suprasellar tuberculoma which presented with central diabetes insipidus, the authors report the frequency of pituitary tuberculoma, its physiopathology, clinical presentation hormonal and radiological findings thus management and evolution. A 42 years old woman, with a history of erythema nodosum, presented with polyuria polydipsia (PUPD), amenorrhea and galactorrhea. Endocrine investigations showed central diabetes insipidus, elevated serum prolactin levels and cortisol failure. Magnetic resonance imagining scans (MRI) revealed a nodular thickening of the pituitary enlargement and loss of posterior pituitary hypointensity signal. Etiologic inquiry has removed the diagnosis of sarcoidosis, Langerhan's histosis, autoimmune hypophysitis and sellar metastasis. The history of erythema nodosum, the positivity of tuberculin skin test and the presence of koch bacillus in the bronchial fluid after culture led to a diagnosis of tuberculosis. Treatment was started with four drug antitubercular chemotherapy regimen for 2 months, and tow drug antitubercular chemotherapy regimen for 16 months. This treatment is associated with hydrocortisone, desmopressin nasal spray and bromocriptine. Under treatment, there was an improvement in clinical condition, disapearence of headache, PUPD and galactorrhea thus normalization of prolactin. A follow-up MRI, 8 months later, showed that pituitary lesion has been completely removed, suggesting our clinical and biology presumption. Pituitary tuberculosis is rare, however, when encountered, they may present a diagnostic difficulty. Accurate diagnosis and management is important because pituitary tuberculoma is curable.     

Ectopic prolactinoma of the sphenoidal sinus: case report

A 34-year-old woman was hospitalized for exploration of amenorrhea and galactorrhea. She had experienced primary sterility, diagnosed 11 years earlier. Endocrine tests demonstrated hyperprolactinemia (serum prolactin 594 ng/ml). Magnetic resonance imaging (MRI) showed a soft tissue mass located within the posterior part of the sphenoidal sinus. The pituitary gland appeared normal. Medical treatment with bromocriptine was unsuccessful. Transsphenoidal tumor resection was performed. Histology reported adenoma, which was consistent with prolactin-producing tumor demonstrated by immunohistochemical staining for prolactin. Because of the persistence of hyperprolactinemia related to an intra-sphenoidal tumor remnant, bromocriptine (15 mg/d) was initiated. Menses ensued and prolactin level declined (49 ng/ml). One year later, the tumor remnant had disappeared on the MRI and the patient became pregnant. Ectopic adenomas of the sphenoidal sinus are of particular interest due to the diagnostic difficulties encountered. Nevertheless, the nature of the lesion can be determined from the endocrine manifestations. Some of these tumors respond to medical treatment, similar to intra sellar tumors. Surgery remains however the only means of obtaining definitive diagnosis and cure.     

Primary hypothyroidism and galactorrhea.

Ten of 16 women with primary hypothyroidism and high thyrotropin (TSH) concentrations had high serum prolactin (PRL) concentrations. A positive correlation was observed between the basal TSH and PRL levels in the hypothyroid patients. Five of these patients complained of persistent galactorrhea after delivery. After treatment with triiodothyronine (T3), the elevated TSH and PRL levels fell to within normal ranges, and the galactorrhea disappeared. It is suggested that the elevated serum PRL levels of patients with primary hypothyroidism are mediated by feedback-induced thyrotropin-releasing hormone (TRH) secretion or an enhanced response to endogenous TRH, and that the combination of delivery and the PRL excess may induce persistent galactorrhea in patients with primary hypothyroidism.     

Cyproheptadine in the management of the galactorrhea-amenorrhea syndrome

We evaluated long-term treatment with the antiserotonergic agent cyproheptadine in the management of the galactorrhea-amenorrhea syndrome. Fifteen women with a mean initial serum prolactin of 37 +/- 7 ng/mL received 16 to 24 mg of cyproheptadine daily; they had a significant decrease in prolactin concentration at 8 and at 16 weeks (P less than 0.01). Gonadotropin responses were variable, but no significant changes were recorded during treatment. Ten of the 15 women had menstrual bleeding while receiving cyproheptadine, seven had decreased galactorrhea, and two had cessation of galactorrhea. The side effects of treatment were transient drowsiness and weight gain. We conclude that long-term treatment of the galactorrhea-amenorrhea syndrome with cyproheptadine is effective in lowering serum prolactin in patients with mildly elevated or normal levels. Its effect on fertility remains to be ascertained.