Primary empty sella syndrome with elevated serum prolactin

A young, adult, white female with long-standing amenorrhea-galactorrhea syndrome and known pituitary enlargement since 1969 is presented. Further evaluation revealed PRL levels elevated in the microadenoma range and an empty sella. The presence of a pituitary adenoma, however, could not be confirmed by our studies. The question now arises--in a young woman desirous of pregnancy, should an induction of ovulation be attempted in view of the elevated serum PRL and an empty sella?     

Bromocryptine therapy in cases of amenorrhea-galactorrhea

Of 28 patients presenting with amenorrhea-galactorrhea, pituitary tumors were confirmed in eight. Six patients had occult hypothyroidism and the rest had an endocrine profile suggestive of pituitary tumor or of an idiopathic etiology. Treatment with bromocryptine resulted in suppression of the inappropriate lactation and restoration of regular menstrual function. In five cases, however, the galactorrhea was only diminished and in four of these cases, normal ovarian function did not return. Of the 19 patients that were seeking fertility and continued the medication for at least 20 days, nine pregnancies resulted. A similar response to bromocryptine was observed regardless of the underlying cause of the amenorrhea-galactorrhea.     

Hyperprolactinemia associated with clinically silent adenomas: endocrinologic and pathologic studies; a report of two cases

Pituitary adenomas containing adrenocorticotropic hormone (ACTH) in one case, and ACTH, beta-lipotropin, and beta-endorphin in the other, were demonstrated in two patients who had amenorrhea-galactorrhea and hyperprolactinemia with no manifestation of Cushing's disease. Neither adenoma contained prolactin (PRL). Initial bromocriptine therapy resulted in cessation of amenorrhea-galactorrhea and normalization of PRL levels. However, there was radiologic evidence of tumor enlargement in both patients. After pituitary adenomectomy, the two patients resumed regular menses and normal PRL dynamics. These patients illustrate the need for bromocriptine therapy for possible enlargement of their pituitary adenomas. The diagnosis of silent corticotroph adenoma should be kept in mind.     

The amenorrhoea-galactorrhea syndrome: present diagnostic and therapeutic perspectives.

Recent progress in the field of radioimmunology, especially as regards prolactin (PRL) assay, as well as the use of new drugs have opened new perspectives for a better understanding of the "amenorrhoea-galactorrhea syndrome" both from the diagnostic and therapeutic points of view. This syndrome which formerly was considered infrequent, is now observed more and more often, perhaps as a result of the more widespread use of drugs such as phenothiazines, reserpine derivatives, alpha-methyldopa and tricyclic antidepressants, as well as owing to the large-scale use of estrogens and above all of estrogen-progestogen contraceptives. The problems of etiopathogenesis and management of the amenorrhea-galactorrhea syndrome are complicated by the fact that a variety of factors are responsible, as is shown also by the classical nosographic classification with the Forbes-Albright syndrome in the presence of a pituitary tumour, the Chiari-Frommel syndrome of amenorrhea-galactorrhea following pregnancy, and the Argonz-del Castillo-Ahumada syndrome in the absence of lither pregnancy or tumor.     

Antecedent factors and outcome in amenorrhea-galactorrhea

One hundred seventeen patients with amenorrhea and galactorrhea or hyperprolactinemia were evaluated with regard to antecedent factors, results of investigations, and management. Full details of the outcome of prolonged follow-up were available for 104 patients. Patients who developed amenorrhea-galactorrhea after withdrawal of oral contraceptives or postpartum had a lower incidence of pituitary adenomas than did those who developed amenorrhea-galactorrhea spontaneously. Six of a total of 40 tumors were detected only during the follow-up period. This study suggests that patients with spontaneous amenorrhea-galactorrhea have a greater risk of developing a detectable pituitary adenoma than do those with postpill or postpartum symptoms. However, patients with a microadenoma are more likely to have had postpill onset of hyperprolactinemia. Plasma prolactin (PRL) in patients with postpill amenorrhea-galactorrhea increased in proportion to the duration of oral contraceptive use.     

Dysthyroidism in the post-partum period

Post-partum dysthyroidism are not well understood by obstetricians, but are rather frequent (5.5% of the cases); they usually are the manifestation of a lympho-plasmocytic thyroidism with auto-immune origin. They are encouraged by a genetic predisposition and sometimes by food with a high iodine content. The disease starts with a phase of early thyreotoxicosis, 1 to 3 months following delivery, then later with hypothyroidism (from the 3rd to the 9th month), associated with menstrual disorders, an amenorrhea-galactorrhea syndrome or still, the occurrence of a goiter. Most of the time, the course is favorable, even in the absence of treatment with spontaneous return to euthyroidism within a few months, although the chance of permanent hypothyroidism is however non negligible. The diagnosis is difficult, and the treatment should be the least aggressive possible: beta-blocker during the thyreo-toxicosis phase, supplemental treatment during the hypothyroidism phase. There is a risk of recurrence during subsequent pregnancies.     

Interdisciplinary Care and a Focus on Fertility Preservation When Multi-cystic Ovaries Cause Ovarian Torsion: A Case of a 9-year-old Girl with Severe,Undiagnosed Hypothyroidism

BackgroundOvarian torsion can occur in Van Wyk Grumbach syndrome, a disorder characterized by severe primary hypothyroidism and ovarian enlargement. To date, all documented cases of torsion in this setting describe oophorectomy, which has significant hormonal and fertility implications.CaseA 9-year-old pubertal girl presented to the emergency room with abdominal pain. Magnetic resonance imaging demonstrated bilateral, multi-cystic ovaries. Operative laparoscopy confirmed unilateral adnexal torsion, and detorsion without oophorectomy was accomplished. Postoperative laboratory tests revealed severe primary hypothyroidism. Ovarian size was reduced with hormone replacement therapy.Summary and ConclusionThis case demonstrates that prompt interdisciplinary intervention and awareness of severe hypothyroidism as a cause of ovarian torsion related to enlarged, multi-cystic ovaries may reduce the rate of oophorectomy, allowing preservation of pediatric patients’ future fertility, and reducing morbidity postoperatively through prompt, long-term thyroid supplementation.     

Current management of the amenorrhea-galactorrhea syndrome

Management of the amenorrhea-galactorrhea syndrome has changed considerably in the last 5 years. Better understanding of the neuroendocrine physiology of the central nervous system in general, and of the hypothalamic-pituitary region in particular, have contributed significantly to our understanding of the pathophysiology of this syndrome. Greater awareness by physicians, improved neuroradiologic techniques, and the development of immunoassays for prolactin have markedly improved our diagnostic abilities. Many more patients are being diagnosed as having a pituitary tumor. The recent introduction of microneurosurgical techniques and the new medications (ergolines) are changing the treatment of this syndrome. Women in the childbearing age--who are affected most often--can expect successful treatment in the majority of cases with resumption of normal menstrual function and fertility. However, certain risks are still posed, particularly during pregnancy. In spite of improved diagnosis and treatment, the natural history of prolactin-secreting pituitary tumors and the long-range effects are still not fully appreciated. More experience in time will be needed before the indications for and the efficacy of various treatment regimens are fully known.     

Dysfunction of dopaminergic regulation of prolactin in patients with functioning and nonfunctioning pituitary adenomas and craniopharyngiomas

The response to domperidone (a dopamine blocking agent) of serum prolactin (PRL) levels was compared in 3 patients with amenorrhea-galactorrhea without evidence of a pituitary tumor, 23 patients with prolactinomas (10 cases with histologic confirmation), 7 patients with histologically verified large nonfunctioning pituitary adenomas with normal or moderately elevated basal PRL levels, and 6 patients with histologically verified craniopharyngiomas (3 with normal basal PRL levels and 3 with elevated PRL levels). The response was compared with that of 10 patients with postpartum hyperprolactinemia and 14 normal women. Ten milligrams of intravenous domperidone induced a rapid rise in PRL that was maximal at 30 to 45 minutes in normal, postpartum, and amenorrhea-galactorrhea patients who had no sign of tumor. In contrast, domperidone failed to induce significant changes in PRL in cases of prolactinoma, nonfunctioning pituitary adenomas, and craniopharyngioma with or without elevated basal PRL levels. The results suggest that dopaminergic control on PRL secretion was impaired in all tumor cases. The mechanisms of this abnormal dopaminergic control, however, may be different. Whereas dopamine control in cases of prolactinoma is altered at the level of pituitary dopamine receptors, alternative explanations must be found for those tumors with normal basal PRL levels and lack of response to domperidone.     

Pregnancy following combined therapy with thyroid hormone and bromocriptine in a patient with amenorrhea-galactorrhea due to primary hypothyroidism

Combined therapy with thyroid hormone (desiccated thyroid) and bromocriptine (CB-154) was applied in a 29-year-old patient with amenorrhea-galactorrhea due to primary hypothyroidism. Two months after commencing administration of desiccated thyroid, the elevated serum level of TSH returned to the normal range while that of PRL remained within the supranormal range (from 134 ng/ml to 86.7 ng/ml). However, it fell to the normal range 2 weeks after administration of CB-154 with thyroid hormone. Subsequently, the galactorrhea completely ceased and ovulatory menstruation resumed with 3 months, and conception was achieved directly after that menstrual period. Only desiccated thyroid was administered during pregnancy and the patient delivered a male infant weighing 2,800 g without difficulty.     

Primary hypothyroidism presenting as ovarian tumor and precocious puberty in a prepubertal girl.

We report a case of a prepubertal girl with juvenile primary hypothyroidism presenting as ovarian cysts and precocious puberty. The 7-year-old female was referred to our clinic because of a pelvic/abdominal mass and vaginal bleeding. Besides these findings, on physical examination we noticed the thyroid gland globally increased and the presence of secondary sexual characteristics. Based upon the clinical profile and investigations, the patient was diagnosed with juvenile primary hypothyroidism due to autoimmune thyroiditis. The cysts and precocious puberty resolved spontaneously after the simple replacement of thyroid hormone. It is important to bear in mind hypothyroidism in cases of girls presenting ovarian cysts and precocious puberty in order to avoid unnecessary surgery on the ovaries.     

Primary hypothyroidism presenting as ovarian tumor and precocious puberty in a prepubertal girl

We report a case of a prepubertal girl with juvenile primary hypothyroidism presenting as ovarian cysts and precocious puberty. The 7-year-old female was referred to our clinic because of a pelvic/abdominal mass and vaginal bleeding. Besides these findings, on physical examination we noticed the thyroid gland globally increased and the presence of secondary sexual characteristics. Based upon the clinical profile and investigations, the patient was diagnosed with juvenile primary hypothyroidism due to autoimmune thyroiditis. The cysts and precocious puberty resolved spontaneously after the simple replacement of thyroid hormone. It is important to bear in mind hypothyroidism in cases of girls presenting ovarian cysts and precocious puberty in order to avoid unnecessary surgery on the ovaries.     

Pituitary tumors

The clinical, therapeutic, and laboratory aspects of pituitary tumors are outlined. Sometimes tumor symptoms like headaches and visual disturbances are not present, while endocrine symptoms depend on the type of trophic cells involved: acromegaly for growth hormone, Cushing syndrome for cortico-melanotrophic hormone, amenorrhea-galactorrhea for prolactin, and rarely, symptoms related to thyrotropin or gonadotropin. Recently prolactin-secreting adenomas have been differentiated from chromophobic adenomas in routine diagnosis. The endocrine symptoms may be masked by estrogen-progestagen pills until tumor symptoms develop, when surgery is mandatory. The results of surgery depend on the tumor volume. Selective adenectomy usually permits normal endocrine function afterward. These tumors may also be treated pharmacologically, e.g., with L-DOPA or dibromoergocryptine. The results of treatment are followed by pre- and postoperative radioimmunoassay of pituitary hormones.     

Spontaneous pregnancy in women with a prolactin-producing pituitary adenoma

The occurrence of spontaneous pregnancy in patients with amenorrhea-galactorrhea, hyperprolactinemia, and radiographic evidence of a pituitary tumor is unusual. We present here two patients who conceived spontaneously. One had an uneventful pregnancy. Following delivery, transsphenoidal pituitary surgery was performed, confirming the presence of a prolactin-producing adenoma. The second patient had an early pregnancy termination (at 12 weeks of gestation). These patients provide evidence that ovulation and pregnancy can occur in spite of elevated prolactin levels.     

Hyperprolactinemia with prolonged amenorrhea reversed with bromocriptine in a menopausal woman

Bromocriptine treatment of the amenorrhea-galactorrhea syndrome with elevated prolactin levels is well recognized. The return of menses after 30 years in a menopausal woman with this syndrome is described. Lowering of both prolactin and follicle-stimulating hormone levels was found to occur after bromocriptine therapy.     

The ubiquitousness of premenstrual tension in gynecologic practice

One hundred thirty-seven premenopausal women with premenstrual tension underwent laparoscopy for bleeding, pain and/or infertility. Endometriosis was the associated gynecologic disease observed most frequently (66 patients). Other associated disorders were primary dysmenorrhea (31), poststerilization syndrome (24), chronic pelvic inflammatory disease (8) and leiomyoma uteri (8). Screening for prolactin and thyroid-stimulating hormone in patients with galactorrhea (74) revealed one patient with pituitary microadenoma and two with primary hypothyroidism. The midluteal progesterone levels were significantly decreased, whereas the midluteal estradiol 17 beta levels were significantly elevated. Because of the frequent association of premenstrual tension with other gynecologic diseases, screening for premenstrual tension in all premenopausal women is recommended.     

Current concepts of prolacting physiology in normal and abnormal conditions.

Currently the physiology and pathophysiology of pituitary prolactin secretion are under intensive investigation. Development of sensitive, specific radioimmunoassays for hPRL and improved roentgenographic techniques have increased the diagnostic acumen for incipient pituitary microadenomas. Several modalities of treatment are available at the present time which can result in improvement in the clinical symptoms of the amenorrheagalactorrhea syndromes. Eponymic classification of amenorrhea-galactorrhea syndromes should be discarded and appropriate diagnostic studies initiated to determine the etiology of the inappropriate breast secretion and/or elevated serum hPRL level.     

Síndrome de Rothmund-Thompson (poiquilodermia atrofica congénita) en mujer gestante

Congenital poikiloderma syndrome, also called Rothmund-Thomson syndrome, is a rare autosomal recessive genodermatosis due to a RECQ4 gene mutation on chromosome 8. This syndrome has a range of clinical manifestations that include poikiloderma, skeletal changes, hypothyroidism and hypogonadism and juvenile cataracts. Although 200 cases of this disease have been documented worldwide, its association with pregnancy has not been previously reported. We report a case of Rothmund-Thomson syndrome in a pregnant patient at term and review the world literature on the topic.