Surgery versus conservative care for Rathke's cleft cyst.

BACKGROUND: Rathke's cleft cysts are benign cystic lesions of the sellar region, which may cause headache, pituitary deficiencies and visual disturbances from mass effect. Their management is not standardized yet. This study is about establishing a consensus for medical care of RCC. MATERIAL AND METHODS: We performed a retrospective observational study of all patients that were diagnosed or followed for RCC between 2008 and 2018 (11 years), in the neurosurgical and the adult endocrine departments of our institution. The study's average time length of follow-up is 72.9 months (from 2 to 385 months). RESULTS: The 57 included patients were divided into 2 groups: group A, which included 39 patients that were conservatively managed and group B, which included 18 surgically treated patients. Group A showed either an improvement or a spontaneous resolution of headaches in 56.1% of the cases (P<0.01); a resolution of hyperprolactinemia in 70% of the cases (P=0.21); and of hypogonadism, ACTH deficiency, growth hormone deficiency in 100% of the cases. There was no spontaneous improvement of visual disturbances (P<0.01) or diabetes insipidus (P=0.29) during follow-up. Regarding group B, surgery allowed improvement or complete resolution of headaches in 60% of the cases; visual troubles in 100% of the cases (P<0.01); and hyperprolactinemia in 100% of the cases. Pituitary deficiencies were not improved by surgery. CONCLUSIONS: This study offers guidance in decision-making regarding the management of RCC patients. Surgery is particularly suitable for treating visual disturbances caused by RCC. Regular follow-up is more appropriate than surgery concerning headaches, hyperprolactinemia, endocrine disruptions and diabetes insipidus.

A case of functioning gonadotroph adenoma in a reproductive aged woman.

A 34-year-old woman presented our hospital with complaint of irregular menstruation and abnormal uterine bleeding lasting for a month. After her second parturition at the age of 27, her menstrual cycle had been regular, but it suddenly became irregular at the age of 30. Transvaginal ultrasound revealed the presence of ovarian mass, and the patient underwent diagnostic laparoscopic surgery. Bilateral ovaries temporally shrink after puncture but the size soon resumed. Gonadotropins were almost normal, but estradiol and PRL levels turned out to be elevated, and cabergoline treatment was initiated. After referral to our hospital, we found that the ovaries showed multifollicular appearance. Brain magnetic resonance imaging showed an 18-mm macroadenoma in the suprasellar area. To suppress the secretion of endogenous gonadotropins and estrogen, low-dose estrogen-progestin was prescribed. Surprisingly, the treatment temporarily reduced the size of the ovaries. The patient was referred to a neurosurgeon, and a functioning gonadotroph adenoma was suspected. After the resection of the pituitary tumor, her menstrual cycle became regular, and the size of bilateral ovaries became normal. We also noticed that her ovarian reserve judged by anti-Müllerian hormone had been almost diminished after the surgical treatment, probably reflecting the exhaustion of follicular pool. Women with multifollicular ovaries and elevated estradiol levels may have functioning gonadotroph adenomas, although the level of FSH is relatively normal, and ovarian reserve can be followed by measuring anti-Müllerian hormone.

Resolution of dopamine agonist-resistant hyperprolactinemia by hysterectomy: a case report.

Prolactin-producing uterine leiomyomas are very rare. Although hyperprolactinemia rapidly improves after removal of such leiomyomas, no preoperative diagnostic test has been established for prolactin-producing uterine leiomyomas. A 45-year-old Japanese woman, gravida 3 para 3, was referred to our hospital for further examination of hyperprolactinemia resistant to a dopamine agonist. A pituitary prolactinoma was undetectable by brain magnetic resonance imaging. A bromocriptine loading test revealed an increased serum prolactin concentration after loading. Examination for the detection of an ectopic prolactinoma revealed a 9.0 cm diameter uterine leiomyoma that had measured 6.6 cm in diameter about six months before the first visit to our hospital. The hyperprolactinemia rapidly improved after hysterectomy. A prolactin-producing uterine leiomyoma should be considered as a possible cause of hyperprolactinemia resistant to dopamine agonists. Responsiveness to dopamine agonists; deterioration of hyperprolactinemia may be diagnostic for prolactin-producing uterine leiomyomas, although further research is required.

Xanthomatous Hypophysitis Presenting with Diabetes Insipidus Completely Cured Through Transsphenoidal Surgery: Case Report and Literature Review.

BACKGROUND: Xanthomatous hypophysitis (XH) is extremely rare. Only 27 cases have been reported in the literature. No XH patient presenting with diabetes insipidus (DI) has been completely cured through surgery. Here, we describe the first XH case of a DI patient whose pituitary function was normalized postoperatively, without hormone replacement therapy. CASE DESCRIPTION: A 41-year-old woman suffered from polydipsia, DI, headache, and breast discharge. Laboratory investigation revealed hyperprolactinemia. Pituitary magnetic resonance imaging showed a 2.0-cm × 1.4-cm × 1.6-cm lesion that demonstrated heterogeneous intensity on T1-weighted imaging and peripheral ring enhancement following contrast; the lesion was totally removed through transsphenoidal surgery. Histopathologic and immunohistochemical examinations confirmed the diagnosis of XH. At the 4- and 15-month follow-up visits, all pituitary-related hormones were normal, and the patient was not taking medication. A repeat pituitary magnetic resonance imaging showed no evidence of recurrence. CONCLUSIONS: To the best of our knowledge, this case is the first documented occurrence of XH with DI completely cured through surgery. If XH is suspected, total surgical resection of the lesion is recommended and normal pituitary tissue should be carefully protected intraoperatively.

Time Course of Resolution of Hyperprolactinemia After Transsphenoidal Surgery Among Patients Presenting with Pituitary Stalk Compression.

BACKGROUND: Primary lactotroph disinhibition, or stalk effect, occurs when mechanical compression of the pituitary stalk disrupts the tonic inhibition by dopamine released by the hypothalamus. The resolution of pituitary stalk effect-related hyperprolactinemia postoperatively has not been studied in a large cohort of patients. We performed a retrospective review to investigate the time course of recovery of lactotroph disinhibition after transsphenoidal surgery. METHODS: Medical records were retrospectively reviewed for all patients undergoing transsphenoidal surgery with the senior author from April 2008 to November 2014. RESULTS: Of 556 pituitary adenomas, 289 (52.0%) were eliminated: 77 (13.9%) had an immunohistochemically confirmed prolactinoma, 119 (21.4%) patients had previous surgery, 93 (16.7%) had incomplete medical records, leaving 267 patients (48.0%) for final analysis. Of these patients, 72 (27.0%) had increased serum prolactin levels (≥23.3 ng/mL), suggestive of pituitary stalk effect (maximum prolactin level = 148.0 ng/mL). Patients with stalk effect were more likely than those with normal serum prolactin levels to present with menstrual dysfunction (29.7% vs. 19.4%; P < 0.01) and galactorrhea (11.1% vs. 2.1%; P < 0.01). Patients with lactotroph disinhibition were more likely to harbor macroadenomas than were patients who did not show lactotroph disinhibition (81.9% vs. 70.2%; P = 0.06). Among patients with increased preoperative prolactin, 77.8% experienced normalization of serum prolactin postoperatively, galactorrhea improved in 100%, sexual dysfunction resolved in 66.6%, and menstrual dysfunction among premenopausal females normalized in 73.3% at last follow-up (mean, 5.35 years; range, 0.1-10 years). CONCLUSIONS: Transsphenoidal surgery can provide durable normalization of serum prolactin levels and related symptoms caused by pituitary stalk compression-related lactotroph disinhibition.

Gonadotroph adenoma causing ovarian hyperstimulation syndrome in a premenopausal woman.

INTRODUCTION: Gonadotroph adenomas occur commonly in middle-aged adults without any specific endocrinological symptoms. To date, only 30 cases of gonadotropinoma causing ovarian hyperstimulation syndrome in pre-menopausal women have been reported. CASE REPORT: A 37-year old woman with pituitary macroadenoma and hyperprolactinaemia was admitted to the Department of Endocrinology, Diabetology and Isotope Therapy. She presented with recurrent ovarian cysts, menstrual disturbances, headaches, visual impairment and galactorrhea. Her endocrine profile showed normal values of FSH, elevated concentrations of estradiol and suppressed LH levels. Transsphenoidal resection of the tumor tissue resulted in normalization of the hormone values and improvement in the clinical picture. CONCLUSIONS: Gonadotroph adenomas should be considered in the differential diagnosis in premenopausal women with OHSS.

The pituitary stalk effect: is it a passing phenomenon?

Most patients with large pituitary tumors do not exhibit hyperprolactinemia as a result of pituitary lactotroph disinhibition (stalk effect). Studies have demonstrated that increased intrasellar pressure is associated with both "stalk effect" hyperprolactinemia and pituitary insufficiency. Our primary hypothesis was that, despite continued disinhibition, lactotroph failure is responsible for normoprolactinemia in patients with large macroadenomas. As a corollary, we proposed that the hyperprolactinemia phase, which presumably would precede the insufficiency/normoprolactinemic state, would more likely be discovered in premenopausal females and go unnoticed in males. Prospective, consecutive surgical series of 98 patients of clinically nonfunctional pituitary adenomas. Lactotroph insufficiency was inferred by the coexistence of insufficiency in another pituitary axis. The existence of pre-operative lactotroph disinhibition was inferred based on comparison of pre- versus post-operative prolactin levels. 87 % of patients with tumor size >20 mm and normoprolactinemia had pituitary insufficiency. Pre-operative prolactin in patients with pituitary insufficiency were lower than those with intact pituitary function. Prolactin levels dropped in nearly all patients, including patients with normoprolactinemia pre-operatively. Premenopausal women had smaller tumors and higher pre-operative prolactin levels compared to males. No premenopausal female exhibited evidence of pituitary insufficiency. Our study provides suggestive evidence that the "stalk effect" pathophysiology is the norm rather than the exception, and that the finding of normoprolactinemia in a patient with a large macroadenoma is likely a consequence of lactotroph insufficiency. In males, the hyperprolactinemia window is more likely to be missed clinically due to an absence of prolactin-related symptoms.

Primary adult infradiaphragmatic craniopharyngiomas: clinical features, management, and outcomes in one Chinese institution.

OBJECTIVE: This study was designed to evaluate the clinical, radiologic, histologic, and surgical outcome characteristics of this disease treated in a single institution. METHODS: Sixteen adult patients underwent transsphenoidal microsurgery from October 2005 to December 2010 at Neurosurgical Center of Beijing Tiantan Hospital. The clinical, radiological, operative, and pathological findings of the patients were reviewed retrospectively. RESULTS: Pituitary dysfunction was presented in 12 patients, visual acuity and/or field deterioration in 11 patients, and headache in 8 patients. Hyperprolactinemia was presented in 7 of 9 female patients. All lesions were resected by transsphenoidal microsurgery as the primary procedure. A gross total resection was achieved in 3 of 16 patients, a radical subtotal resection in the remaining 13 patients. Nine cases were histologically classified as adamantinous subtype. After a mean follow-up of 50 months, 2 patients experienced recurrence. All female patients who had hyperprolactinemia experienced a gain of function postoperatively. Six patients experienced new diabetes insipidus. Visual field improved or normalized in 8 of 9 patients. Visual acuity improved in 1 case, and worsened in 1 patient. CONCLUSIONS: Primary adult infradiaphragmatic craniopharyngiomas are relatively rare lesions occurring in young adults. Pituitary dysfunction, visual acuity and/or field deterioration, and headache were the most common chief symptoms. Transsphenoidal surgery, including tearing the cyst walls off the diaphragma sellae and protecting normal pituitary tissue as much as possible, is recommended. Although at the risk of impairing the function of anterior pituitary, transsphenoidal surgery results in a high rate of both visual field and hyperprolactinemia improvement with a low associated risk of recurrence. In terms of pathological aspects, the adamantinous subtype was more common.

Pituitary surgery for small prolactinomas as an alternative to treatment with dopamine agonists.

Despite the fact that consensus guidelines recommend long-term dopamine agonist (DA) therapy as a first-line approach to the treatment of small prolactinoma, some patients continue to prefer a primary surgical approach. Concerns over potential adverse effects of long-term medical therapy and/or the desire to become pregnant and avoid long-term medication are often mentioned as reasons to pursue surgical removal. In this retrospective study, 34 consecutive patients (30 female, 4 male) preferably underwent primary pituitary surgery without prior DA treatment for small prolactinomas (microprolactinoma 1-10 mm, macroprolactinoma 11-20 mm) at the Department of Neurosurgery, University of Bern, Switzerland. At the time of diagnosis, 31 of 34 patients (91%) presented with symptoms. Patients with microprolactinomas had significantly lower preoperative prolactin (PRL) levels compared to patients with macroprolactinomas (median 143 µg/l vs. 340 µg/l). Ninety percent of symptomatic patients experienced significant improvement of their signs and symptoms upon surgery. The postoperative PRL levels (median 3.45 µg/l) returned to normal in 94% of patients with small prolactinomas. There was no mortality and no major morbidities. One patient suffered from hypogonadotropic hypogonadism after surgery despite postoperative normal PRL levels. Long-term remission was achieved in 22 of 24 patients (91%) with microprolactinomas, and in 8 of 10 patients (80%) with macroprolactinomas after a median follow-up period of 33.5 months. Patients with small prolactinomas can safely consider pituitary surgery in a specialized centre with good chance of long-term remission as an alternative to long-term DA therapy.

Dopaminergic resistant prolactinomas in the peripubertal population.

We report two children with macroadenomas and hyperprolactinemia resistant to medical therapy using dopamine agonists, who experienced secondary pituitary dysfunction. Both required surgical debulking, and one has received growth hormone treatment with no increase in tumor size.

[Transsphenoidal approach to prolactinomas]. / Cirugia transeptoesfenoidal en adenomas hipofisarios productores de prolactina.

INTRODUCTION: Transeptal transsphenoidal surgery for pituitary tumors is a well established surgical technique. In particular the use of medical treatment in patient with prolactinomas has induced the control of hiperprolactinemia and the shrinkage of the tumor in the great majority of the patients, for that reason the treatment of the prolactinomas is controversial. OBJECTIVE: We evaluate the results of transsphenoidal microsurgical treatment of prolactin secreting adenomas at our Unit. METHODS: We made a retrospective analysis of 63 patients operated on via transsphenoidal microsurgical technique for prolactin secreting adenomas between 1996 and 2003. Age, sex, symptoms, tumor size, hormonal levels, complications and postsurgical outcome were considered. RESULTS: There was a female predominance of 86% of the cases and middle aged patients were more commonly seen. 31 patients had tumors more than 10mm in diameter on the CT scan. The most frecuent complication was transient diabetes insipidus (11 cases). Prolactin levels were reduced to non tumoral values in 90.6% of microadenomas (29 cases) and in 67.7% of macroadenomas (21 cases). Headache was the most frecuent complain in our patients with amelioration after surgery in 82% (36 cases). Campimetric visual defects were reduced in 69% (18 cases). CONCLUSIONS: Transsphenoidal adenomectomy is a safe treatment option for patients with prolactin secreting adenomas with surgical indication.

Concurrent lymphocytic hypophysitis and pituitary adenoma. Case report and review of the literature.

Lymphocytic hypophysitis (LyH) is an uncommon intrasellar lesion characterized by lymphocytic infiltration of the adenohypophysis. Evidence suggests that the cause is autoimmune, and the symptoms are usually related to either a mass effect or endocrine dysfunction. Lymphocytic hypophysitis has been described rarely in the setting of other simultaneous pathological processes that involve the pituitary and sella turcica, and is postulated to arise from an intrinsic inflammatory response. The authors report the case of a 43-year-old woman who presented with a 2-month history of galactorrhea and pseudohyperprolactinemia secondary to a 10-mm lesion within an enlarged pituitary gland. She was nulliparous and had no contributory medical history. Serial neuroimaging performed over a 2-year period demonstrated lesion growth, and visual deficits had developed; together these warranted surgical intervention. A transsphenoidal resection was performed. Microscopic and immunohistopathological examinations revealed a nonsecreting pituitary adenoma with concurrent lymphocytic adenohypophysitis. This is the first documented case of LyH in the setting of a null-cell pituitary adenoma. The authors review the related literature and outline potential mechanisms for the concurrent development of LyH and a pituitary adenoma.

Hyperprolactinaemia in 271 women: up to three decades of clinical follow-up.

OBJECTIVE: To characterize women with hyperprolactinaemia at diagnosis and to assess the effect of treatment after long duration of the disease. DESIGN: Retrospective chart review. PATIENTS AND MEASUREMENTS: Two hundred and seventy-one women with hyperprolactinaemia at the Karolinska University Hospital, Stockholm, Sweden between 1974 and 2002 were evaluated retrospectively. Criterion for inclusion was elevated S-PRL (> or = 20 microg/l) found on at least two occasions. Secondary hyperprolactinaemia was excluded. The patients were followed for a median time period of 111 (6-348) months. Two hundred and forty patients were treated with dopamine agonists, 17 underwent surgery, seven received radiotherapy and seven were followed without treatment. RESULTS: Mean age at diagnosis was 31 (+/- 9.5) years and median PRL level was 72 (25-3500) microg/l. Menstrual disturbances were present in 87% of the women of reproductive age and 47% had galactorrhoea. Microadenomas were found in 63%, macroadenomas in 8% and idiopathic hyperprolactinaemia in 29%. Patients with menstrual disturbances had higher PRL levels than women with normal menstrual function (P < 0.001). We found no differences in PRL levels between patients with or without galactorrhoea (P = 0.578). At the end of clinical follow-up, menstrual cycle was normalized in 94% and galactorrhoea disappeared in 94%. In the medically treated patients, median PRL levels decreased from 70 (25-3100) to 13 (0-89) microg/l, (P < 0.0001). Normalization of PRL level was achieved in 71% of the patients and 80% showed a total or partial degree of tumour shrinkage. In the surgically treated patients, 53% had normal PRL levels without medication at follow-up. CONCLUSION: Medical treatment was effective in correcting hypogonadism, normalizing PRL levels and reducing tumour size in the majority of the patients after short-term treatment and also in the long run. However, the possibility of transsphenoidal surgery in specific cases must be considered.

Complete remission of hyperprolactinemia and erythrocytosis after hysterectomy for a uterine fibroid in a woman with a previous diagnosis of prolactin-secreting pituitary microadenoma.

A 44-year-old woman who had been suffering for 10 years from amenorrhea and hyperprolactinemia resistant to high doses of bromocriptine was hospitalized with erythrocytosis, normal serum erythropoietin (sEpo) levels, and hypertension. Erythrocytosis secondary to uterine myoma and a prolactin-secreting pituitary microadenoma were initially diagnosed. The hyperprolactinemia was bromocriptine resistant, despite gradual increase of the dosage to 30 mg/day. Both hyperprolactinemia and erythrocytosis unexpectedly regressed completely after the patient underwent hysterectomy for a uterine fibroid 9 months after the erythrocytosis was first disclosed. Given the well-known effects of prolactin on hematopoietic cells, we hypothesize that--in this very unusual case--the two main, apparently unrelated abnormalities (erythrocytosis with normal sEpo levels and hyperprolactinemia) may have been the clinical consequence of the functional redundancy and pleiotropy of the "pituitary" hormone prolactin, inappropriately secreted by a uterine fibroid for more than 10 years.

Preoperative identification of clearly separated double pituitary adenomas.

OBJECTIVE: Double pituitary adenomas are extremely rare. They can be divided into contiguous and clearly separated types. Most contiguous tumours are surgically removed as one tumour and the co-existence of different adenoma types can be confirmed by histological methods. In contrast, detailed preoperative neuroimaging studies can suggest the co-existence of separated multiple adenomas. In patients with multiple adenomas, surgical failure may result when one adenoma is missed during surgery. Among 600 surgical cases we encountered four patients with clearly separated double pituitary adenomas; all were highly suspect on preoperative MRI studies. PATIENTS AND RESULTS: All four patients manifested acromegalic symptoms; one patient also exhibited hyperprolactinemia and two had familial pituitary adenomas unrelated to multiple endocrine neoplasia type I (MEN-1). All underwent transsphenoidal surgery and histology confirmed the diagnosis of GH-producing plus gonadotroph adenoma in two cases and of two GH-producing adenomas each in the other two patients. CONCLUSION: Although the pathogenesis of our double adenomas remains unknown, genetic abnormalities may be involved because two patients had familial pituitary adenomas unrelated to MEN-1. When preoperative MRI is suggestive of double adenomas, careful surgical exploration is necessary to avoid missing the other adenoma because the risk of surgical failure is high, especially in patients with functioning adenomas.