Trans-sphenoidal surgery for microprolactinoma: an acceptable alternative to dopamine agonists? (1/259)

AIMS: Reported cure rates following trans-sphenoidal surgery for microprolactinoma are variable and recurrence rates in some series are high. We wished to examine the cure rate of trans-sphenoidal surgery for microprolactinoma, and to assess the long-term complications and recurrence rate. DESIGN: A retrospective review of the outcome of trans-sphenoidal surgery for microprolactinoma, performed by a single neurosurgeon at a tertiary referral centre between 1976 and 1997. PATIENTS: All thirty-two patients operated on for microprolactinoma were female, with a mean age of 31 years (range 16-49). Indications for surgery were intolerance of dopamine agonists in ten (31%), resistance in six (19%) and resistance and intolerance in four (12.5%). Two patients were from countries where dopamine agonists were unavailable. RESULTS: The mean pre-operative prolactin level was 2933 mU/l (range 1125-6000). All but 1 had amenorrhoea or oligomenorrhoea, with galactorrhoea in 15 (46.9%). Twenty-five (78%) were cured by trans-sphenoidal surgery, as judged by a post-operative serum prolactin in the normal range. During a mean follow-up of 70 months (range 2 months to 16 years) there was one recurrence at 12 years. Post-operatively, one patient became LH deficient, two patients became cortisol deficient and two became TSH deficient. Out of 21 patients tested for post-operative growth hormone deficiency, 6 (28.6%) were deficient. Five patients developed post-operative diabetes insipidus which persisted for greater than 6 months. There were no other complications of surgery. The estimated cost of uncomplicated trans-sphenoidal surgery, and follow-up over 10 years, was similar to that of dopamine agonist therapy. CONCLUSION: In patients with hyperprolactinaemia due to a pituitary microprolactinoma, transsphenoidal surgery by an experienced pituitary surgeon should be considered as a potentially curative procedure. The cost of treatment over a 10 year period is similar in uncomplicated cases to long-term dopamine agonist therapy.  (+info)

Increased episodic release and disorderliness of prolactin secretion in both micro- and macroprolactinomas. (2/259)

To quantify prolactin (PRL) secretion patterns, ten untreated (female) microprolactinoma patients and six (male) macroprolactinoma patients underwent repetitive blood sampling every 10 min over 24 h. PRL release activity was analyzed from plasma PRL concentration (immunofluorimetric assay) profiles via a model-independent discrete peak detection program (Cluster) and a waveform-independent deconvolution technique (Pulse). Diurnal variations were analyzed by cosinor analysis. The number of distinct PRL pulses (mean +/- S.E.M.) was increased in patients: microprolactinoma 18.6 +/- 0.6/24 h versus female controls 12.4 +/- 0.6 (P = 6.7 x 10-s), and macroprolactinoma 18.0 +/- 0.9 versus male controls 13.5 +/- 0.8/24 h (P = 0.003). In patients, PRL pulse height, amplitude, pulse area and interpeak nadir concentrations were each greatly elevated compared with gender-matched controls. By 2-component deconvolution analysis, the mean nadir PRL secretion rate in microprolactinoma patients was augmented 20-fold at 0.408 +/- 0.089 microgram/l per min versus in female controls 0.019 +/- 0.009 microgram/l per min (P < 0.001); and in macroprolactinoma by 130-fold at 2.067 +/- 0.693 micrograms/l per min versus male controls 0.016 +/- 0.001 microgram/l per min (P = 0.001). Corresponding 24 h mean PRL secretion rates were in women, 0.658 +/- 0.147 and 0.044 +/- 0.018 (P < 0.001), and in men, 3.309 +/- 1.156 and 0.035 +/- 0.010 micrograms/l per min (P = 0.001), being respectively 15- and 94-fold increased in tumors. The estimated PRL production per day was 160 +/- 15 and 187 +/- 20 micrograms in male and female controls respectively. PRL production was 2860 +/- 640 micrograms in female patients with microadenomas (P < 0.001), and 37,800 +/- 5900 micrograms in male macroadenoma patients (P = 0.001). Cosinor analysis of the plasma concentrations revealed a significant rhythm in nine of ten, patients with a microadenoma, and in five of six with a macroadenoma. The same method applied to pulse height and amplitude disclosed a significant rhythm for PRL pulse height, but not for pulse amplitude, suggesting preserved rhythmicity of baseline interpulse nadir PRL concentrations. Approximate entropy (ApEn), a scale- and model-independent regularity statistic, averaged 1.6559 +/- 0.028 in microprolactinoma patients versus 0.8128 +/- 0.079 in female controls (P = 1.7 x 10(-8)); ApEn in macroadenomas was 1.5674 +/- 0.054 versus male controls 0.8773 +/- 0.076 (P = 1.7 x 10(-5), signifying greater secretory irregularity in the patients. Compared with microadenomas, macroadenomas exhibited a higher mean plasma concentration, overall mean PRL secretion rate, nadir secretion rate and pulse area, but similar peak frequency. We conclude that PRL secretion by prolactinomas is characterized by increased plasma PRL episodicity of release, increased total (15- to 100-fold) and basal (20- to 130-fold) secretion rates, and increased disorderlines of minute-to-minute secretion. These abnormalities of secretory control are very similar to those for GH and ACTH identified earlier in acromegaly and Cushing's disease respectively, thus suggesting mechanistic generality of pituitary tumor secretory derangements, independent of the particular hormone.  (+info)

Pituitary tumours in the elderly: a 20 year experience. (3/259)

The proportion of the elderly in the population is increasing, and the appreciation and management of medical problems in this age group will therefore become more important. We therefore decided to determine the clinical features and types of pituitary tumour presenting in the elderly, and to examine the treatment and outcome in this group. We conducted a retrospective case-note review from a specialist endocrine and neurosurgical unit in a tertiary referral centre. Eighty-four patients aged 65 years and over on diagnosis of a pituitary tumour were referred to the unit between 1975 and 1996. There were 45 males and 39 females, and the mean age was 72.4 years (range 65-86). Over half of the pituitary lesions were non-functioning adenomas (NFAs) (60.7%). GH-secreting tumours were present in 11 (13.1%) and macroprolactinomas in 7 (8.1%). Four patients had microadenomas and 17 had miscellaneous pituitary-related lesions. Visual deterioration was the commonest mode of presentation in 33 (39.3%), but 54 (64.3%) had evidence of visual impairment on detailed examination. Despite the majority of patients (80.8%) having coexisting medical conditions, trans-sphenoidal surgery was performed in 60 (71.4%) and was well tolerated with a zero peri- and post-operative mortality rate, and post-operative complications in 11 (13.1%). Pituitary tumours in the elderly are most frequently NFAs that present with visual deterioration and hypopituitarism. The fact that 46.5% were pan-hypopituitary on diagnosis and that 64.3% of patients had visual impairment suggests a delay in diagnosis in this age group. Despite significant coexisting medical pathology in this large series of patients, surgery was safe and successful in the majority.  (+info)

Mitogen-activated protein kinase activation by stimulation with thyrotropin-releasing hormone in rat pituitary GH3 cells. (4/259)

We examined whether mitogen-activated protein (MAP) kinase is activated by thyrotropin-releasing hormone (TRH) in GH3 cells, and whether MAP kinase activation is involved in secretion of prolactin from these cells. Protein kinase inhibitors--such as PD098059, calphostin C, and genistein--and removal of extracellular Ca2+ inhibited MAP kinase activation by TRH. A cAMP analogue activated MAP kinase in these cells. Effects of cAMP on MAP kinase activation were inhibited by PD098059. TRH-induced prolactin secretion was not inhibited by levels of PD098059 sufficient to i activation but was inhibited by wortmannin (1 microM) and KN93. Treatment of GH3 cells with either TRH or cAMP significantly inhibited DNA synthesis and induced morphological changes. The effects stimulated by TRH were reversed by PD098059 treatment, but the same effects stimulated by cAMP were not. Treatment of GH3 cells with TRH for 48 h significantly increased the prolactin content in GH3 cells and decreased growth hormone content. The increase in prolactin was completely abolished by PD098059, but the decrease in growth hormone was not. These results suggest that TRH-induced MAP kinase activation is involved in prolactin synthesis and differentiation of GH3 cells, but not in prolactin secretion.  (+info)

A novel germline mutation of multiple endocrine neoplasia type 1 (MEN1) gene in a Japanese MEN1 patient and her daughter. (5/259)

Familial multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant inherited disorder characterized by tumors of the parathyroid, anterior pituitary and gastro-entero-pancreatic endocrine tissues. The MEN1 gene has recently been cloned and its germline mutations have been considered to play an important role in the tumorigenesis of MEN1. We analyzed a Japanese MEN1 patient and her daughter for germline mutations of the MEN1 gene. The proband (60 y.o.) had primary hyperparathyroidism (PHP) and gastrinoma, and her daughter (30 y.o.) had prolactinoma. Clinical examinations revealed no evidence of PHP in the daughter. We identified a novel heterozygous germline mutation (712 A del) at codon 201 in exon 3 of the MEN1 gene in the proband. Restriction digestion analysis revealed the same mutation pattern in her daughter. These findings suggest that this family has familial MEN1 including a rare case of MEN1 with a single lesion of the pituitary. Genetic examinations are useful as diagnostic tools for any rare or variant case of familial MEN1.  (+info)

Giant insulinoma in a patient with multiple endocrine neoplasia-type I: a case report. (6/259)

We report a case of giant cystic insulinoma constituting part of multiple endocrine neoplasia (MEN) type I. A 29-year-old Japanese man presented with a history of recurrent hypoglycemic attacks. Endocrine examination showed hyperinsulinemia discordant with hypoglycemia, and a giant cystic insulinoma (11 x 10 cm) located in the pancreatic tail was detected radiologically. Hyperprolactinemia due to pituitary adenoma and hyperparathyroidism due to parathyroid hyperplasia were also present. The insulinoma, prolactinoma and hyperplastic parathyroid gland were surgically removed. Fluorescent microsatellite analysis detected loss of heterozygosity (LOH) in chromosome 11q13 in DNA samples from all resected tissues but not from white blood cells. This is a rare case of MEN type I because of the giant cystic insulinoma and the evidence of common LOH detected in all MEN type I tissues.  (+info)

Galactorrhoea and pituitary mass: a typical prolactinoma? (7/259)

A 21 year old woman presenting with galactorrhoea, hyperprolactinaemia, and a pituitary mass on magnetic resonance imaging (MRI) is described who was referred to us before planned pituitary surgery. Although a thorough history did not suggest hypothyroidism, laboratory studies revealed profound primary hypothyroidism. At that time, pituitary MRI showed homogeneous enlargement of the pituitary gland consistent with pituitary hyperplasia due to primary hypothyroidism. With thyroid hormone replacement therapy the galactorrhoea resolved, concentrations of prolactin and thyroid hormones returned to normal, and the pituitary shrunk to normal size within two months. This case illustrates that primary hypothyroidism can present only with galactorrhoea and pituitary mass, and should therefore be considered in the differential diagnosis of hyperprolactinaemia and pituitary enlargement.  (+info)

Proliferation, bcl-2 expression and angiogenesis in pituitary adenomas: relationship to tumour behaviour. (8/259)

The prediction of pituitary tumour behaviour, in terms of response to treatment from which can be derived optimal management strategies, is a challenge that has been approached using several different means. Angiogenesis in other tumour types has been shown to be correlated with poor response to treatment and tumour recurrence. The aim of this paper is to assess the role of measurements of cell proliferation and angiogenesis in predicting pituitary tumour behaviour. The proliferative capacity of the tumour was assessed using the Ki-67 labelling index (LI) while bcl-2 expression was used to assess anti-apoptotic pathways. The microvessel density (MVD) was assessed using antibodies to CD31 and factor VIII-related antigen, and with biotinylated ulex europaeus agglutinin I. There was no difference between Ki-67 LI and MVD of functionless tumours that recurred and those that did not, but bcl-2 expression was significantly lower in tumours that subsequently regrew. Macroprolactinomas had significantly higher LI than microprolactinomas and than all other tumours. Cell proliferation and angiogenesis were not related, showing that both processes are under different control mechanisms in pituitary tumours. In contrast there was a positive relationship between markers of angiogenesis and bcl-2 expression in prolactinomas, GH-secreting tumours and non-recurrent functionless tumours with higher levels of bcl-2 expression being found in the more vascular tumours. These findings may suggest that angiogenesis is related to the ability of tumour cells to survive rather than their proliferative activity.  (+info)