The primary empty sella an endocrine study on 12 cases

Twelve patients (10 women and 2 men) with a primary empty sella turcica were studied. Endocrine function tests were performed as follows: growth hormone (GH) was measured after insulin-induced-hypoglycaemia, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) after LH-releasing hormone, thyrotrophin (TSH) and prolactin after thyrotrophin-releasing hormone; pituitary reserve of adrenocorticotrophin (ACTH) was determined by measurement of plasma cortisol after lysine-vasopressin and 11 deoxycortisol after metyrapone. Five of the patients (group A) had no endocrine disturbance. Seven patients (group B) had a hypothalamo-pituitary disorder. Two of them had panhypopituitarism which appeared in one case after meningoencephalitis and in the other after a severe cranial trauma. In two cases an amenorrhoea-galactorrhoea syndrome with increased prolactin level (68 and 230 ng/ml) led to a diagnosis of a prolactin producing adenoma, which was confirmed by surgery. Finally three cases of amenorrhoeagalactorrhoea, with normal prolactin level, and/or diabetes insipidus remained unexplained. However, no causal relationship could be demonstrated between the pituitary disturbance and the "empty sella". Primary empty sella turcica is therefore a neuroanatomical and neuroradiological entity with no endocrine implication. A pituitary disorder might suggest a microadenoma or an incidentally associated disease.     

Presaccadic omnidirectional burst activity in the basal interstitial nucleus in the monkey cerebellum

The endocrine function and pituitary imaging in Sheehan's syndrome more than 30 years after causative events were evaluated. Magnetic resonance imaging (MRI), a combined anterior pituitary test, plasma vasopressin-to-osmolality adaptation study, and antithyroid and antipituitary cell antibody measurement were performed in 6 women with Sheehan's syndrome. The interval from delivery to the onset of symptoms of hormonal deficiency ranged from 3 to 32 years. Since clinical onset, all had received glucocorticoid and thyroid replacement therapy. Cranial MRI examination showed an "empty sella" in 5 cases. Among these, 2 of 5 (40%) demonstrated panhypopituitarism and the other 3 (60%) maintained gonadotropin response. The pituitary gland was normally discernible but with a low-intensity lesion on T1-weighted images in a patient who maintained PRL and gonadotropin responses. Posterior pituitary function was abnormal in 3 of 6 (50%) despite the absence of polyuria. No antipituitary antibodies were detected in any of the cases. Thyroid peroxidase antibody was negative in all cases, but antithyroglobulin antibody was detected in 2 of 6 (33%). Thyroid-stimulating antibody was not detected, but one case had an anti-TSH antibody. Thirty years after the initial events, most patients with Sheehan's syndrome showed signs of an empty sella on MRI, all having noticeable suppression of anterior and/or posterior pituitary hormones with no related autoimmunity.     

CT abnormalities of the pituitary in hyperprolactinaemic women with normal or equivocal sellae radiologically

Sixteen young women with hyperprolactinaemia and normal or equivocal sella in radiographs underwent computed tomography using a Siemens Somatom II. In all but one case an abnormality was found. The sella was full in seven and partially empty in nine. A tumour was visible in six of the full and in four of the partially empty sellae. All but one of the 10 tumours was unilateral, and in seven the pituitary stalk was deviated away from the tumour. After administration of intravenous contrast (Urografin) four tumours showed diffuse enhancement, four ring enhancement, and two enhanced less than adjacent normal pituitary tissue. Two of the tumours have been subsequently shown histologically to be prolactinomas. Prolactin response to thyrotrophin-releasing hormone predicted a tumour in seven out of eight with visible tumours but also in three out of four without visible tumours; using metoclopramide, a tumour was predicted in six out of seven with tumours, but again in three out of four without visible tumours. Such results question the value of dynamic tests for the discrimination of tumours. We conclude that practically all women with sustained hyperprolactinaemia and a normal or equivocal sella radiologically have pituitary disease.     

"Born from the flank"--discussion concerning "cesarean section" in animals in the Talmud

We determined growth hormone (GH) and insulin-like growth factor I (IGF-I) levels after a 3 h infusion of escalating doses of growth hormone-releasing hormone (GHRH(1-29)) followed by a bolus injection in hypopituitary patients with marked differences in pituitary features at magnetic resonance imaging (MRI) in order to evaluate further the contribution of MRI in the definition of pituitary GH reserve in GH-deficient patients. Twenty-nine patients (mean age 14.5 +/- 4.0 years) were studied. Group I comprised 13 patients: seven with isolated GH deficiency (IGHD) (group Ia) and six with multiple pituitary hormone deficiency (MPHD) (group Ib) who had anterior pituitary hypoplasia, unidentified pituitary stalk and ectopic posterior pituitary at MRI, Group II consisted of eight patients with IGHD and small anterior pituitary/empty sella, while in group III eight had IGHD and normal morphology of the pituitary gland. Growth hormone and IGF-I levels were measured during saline infusion at 08.30-09.00 h, as well as after infusion of GHRH (1-29) at escalating doses for 3h: 0.2 micrograms/kg at 09.00-10.00 h, 0.4 micrograms/kg at 10.00-11.00 h, 0.6 micrograms/kg at 11.00-12.00 h and an intravenous bolus of 2 micrograms/ kg at 12.00 h. In the group I patients, the peak GH response to GHRH(1-29) was delayed (135-180 min) and extremely low (median 2mU/l). In group II it was delayed (135-180 min), high (median 34.8 mU/l) and persistent (median 37.4 mU/l at 185-210 min). In group III the peak response was high (median 30.8 mU/l) and relatively early (75-120 min) but it declined rapidly (median 14.4 mU/l at 185-210 min). In one group I patient, GH response increased to 34.6 mU/l. The mean basal value of IGF-I levels was significantly lower in group I (0.23 +/- 0.05 U/ml) than in groups II (0.39 +/- 0.13U/ ml, p < 0.01) and III (1.54 +/- 0.46 U/ml, p < 0.001) and did not vary significantly during the GHRH(1-29) infusion. The present study demonstrates that the impaired GH response to 3 h of continuous infusion of escalating doses of GHRH(1-29) was strikingly indicative for pituitary stalk abnormality, strengthening the case for use of GHRH in the differential diagnosis of GH deficiency. The low GH response, more severe in MPHD patients, might be dependent on the residual somatotrope cells, while the better response (34.6 mU/l) in the group Ia patients might suggest that prolonged GHRH infusion could help in evaluating the amount of residual GH pituitary tissue. Pituitary GH reserve, given the GH response to GHRH infusion in GH-deficient patients with small anterior pituitary/empty sella, seems to be maintained.     

Prolactin-secreting pituitary tumor in early adolescence: hormonal and electron microscopical studies

A 13-year-old boy was evaluated for an enlarged sella. There were no consistent visual field defects, and carotid arteriograms and pneumoencephalograms showed no extrasellar abnormality. The endocrine workup demonstrated a subnormal growth hormone reserve. The only other, but most striking abnormality, was an excessively high serum prolactin level, which was partially suppressed with levodopa. A chromophobe pituitary tumor was removed that had histological features suggestive of malignant neoplasm. Characteristics of a prolactin-secreting tumor were confirmed by electron microscopy. The serum prolactin levels decreased substantially after surgery and further after a course of pituitary irradiation; however, they continue to be elevated above normal. Prolactin determinations play in integral part in the evaluation for a possible pituitary tumor-not only for diagnostic purposes, but also to provide a parameter of future tumor activity in an established case. Electron microscopical studies are helpful in identifying the tumor as source of the excessive prolactin secretion.     

Transnasal hypophysectomy

A transnasal trans-sphenoidal surgical approach to the pituitary gland is described. The operative and post-operative experiences with the use of this technique on 21 patients with hormone-dependent malignant disease are reported. In 2 patients the procedure was abandoned because of intrasellar haemorrhage and in 1 an empty sella was found. Fifteen patients developed diabetes insipidus and 1 patient died in the postoperative period.     

Human fetal pituitary gland in holoprosencephaly and anencephaly

The normal prenatal development of the human pituitary gland and the gland-supporting sella turcica has recently been investigated. The sella turcica area constitutes a developmental boundary area in the cranial base. Posterior to the area the cranial base has developed close to the notochord, and anterior to the region the cranial base development is dependent chiefly on neural crest cell migrations. In the present study the sella turcica region was analyzed in two fetuses with holoprosencephaly (cyclopia and median cleft) and four fetuses with anencephaly combined with rachischisis in the neck region (GA 16-20 weeks). The sella turcica region was investigated radiologically and histologically. Adenohypohyseal gland tissue was localized by immunohistochemical hormonal marking. In both types of malformation an open craniopharyngeal canal was seen in the base of the sella turcica with adenohypophyseal glandular tissue located in the sella turcica, in the canal, and in the pharyngeal connective tissue at the external side of the cranial base. In conclusion, severe malformations of the pituitary gland occur in both holoprosencephaly, which is a polytopic field defect located anterior to the sella turcica, and in anencephaly associated with notochordal insufficiency posterior to the sella turcica. This might indicate that the sella turcica area, bounding different developmental fields, is involved in various craniofacial malformations. It is consequently recommended that examination of the pituitary gland should become a part of the routine autopsy of prenatal material when malformations in the face, brain, and cranial base occur.     

Assessment of pituitary function after transsphenoidal hypophysectomy in beagle dogs

Pituitary function was assessed in healthy adult beagle dogs before and after hypophysectomy. Anterior pituitary function was tested by use of the combined anterior pituitary (CAP) function test, which consisted of sequential 30-sec intravenous injections of four hypothalamic releasing hormones, in the following order and doses: 1 microgram of corticotropin-releasing hormone (CRH)/kg, 1 microgram of growth hormone-releasing hormone (GHRH)/kg, 10 micrograms of gonadotropin-releasing hormone (GnRH)/kg, and 10 micrograms of thyrotropin-releasing hormone (TRH)/kg. Plasma samples were assayed for adrenocorticotropin (ACTH), cortisol, GH, luteinizing hormone (LH), and prolactin (PRL) at multiple times for 120 min after injection. Pars intermedia function was assessed by the alpha-melanotropin (alpha-MSH) response to the intravenous injection of the dopamine antagonist haloperidol in a dosage of 0.2 mg/kg. Posterior pituitary function was assessed by the plasma vasopressin (AVP) response to the intravenous infusion of 20% saline. Basal plasma ACTH, cortisol, thyroxine, LH. PRL, and AVP concentrations were significantly lower at 10 wk after hypophysectomy than before hypophysectomy. In the CAP test and the haloperidol test, the peaks for the plasma concentrations of ACTH, cortisol, GH, LH, PRL, and alpha-MSH occurred within 45 min after injection. At 2 and 10 wk after hypophysectomy, there were no responses of plasma GH, LH, PRL, and alpha-MSH to stimulation. In four of eight hypophysectomized dogs, there were also no plasma ACTH and cortisol responses, whereas in the other four dogs, plasma ACTH and cortisol responses were significantly attenuated. The basal plasma ACTH and cortisol concentrations were significantly lower in the corticotropic nonresponders than in the responders. Plasma AVP responses were completely abolished by hypophysectomy, although water intake by the dogs was normal. Histopathological examinations at 10 wk after hypophysectomy revealed that adrenocortical atrophy was much more pronounced in the corticotropic nonresponders than in the responders. No residual pituitary tissue was found along the ventral hypothalamic diencephalon. However, in all hypophysectomized dogs that were investigated, islets of pituitary cells were found embedded in fibrous tissue in the sella turcica. A significant positive correlation was found between the number of ACTH-immunopositive cells and the ACTH increment in the CAP test at 10 wk after hypophysectomy. It is concluded that 1) stimulation of the anterior pituitary with multiple hypophysiotropic hormones, stimulation of the pars intermedia with a dopamine antagonist, and stimulation of the neurohypophysis with hypertonic saline do not cause side effects that would prohibit routine use, 2) in the routine stimulation of the anterior pituitary and the pars intermedia, blood sampling can be confined to the first 45 min, 3) the ACTH and cortisol responses to hypophysiotropic stimulation are the most sensitive indicators for residual pituitary function after hypophysectomy, 4) small islets of pituitary cells in the sella turcica, containing corticotropic cells, are the most likely source of the attenuated corticotropic response that may occur after hypophysectomy, and 5) residual AVP release from the hypothalamus after hypophysectomy is sufficient to prevent diabetes insipidus, despite the fact that the AVP response to hypertonic saline infusion is completely abolished.     

Isolated ACTH deficiency

The isolated ACTH deficiency is a scarcely diagnosed disease of heterogeneous nature. Two patients with isolated deficiency of ACTH in whom the initial diagnosis was of primary suprarrenal failure are reported. In the first case this diagnosis was performed after hospital admission for deterioration of the level of consciousness and the development of an acute suprarrenal crisis in the course of nosocomial pneumonia. In the second case the clinical manifestations began as weakness, anorexia, weight loss and lymphocytosis with eosinophilia. In both patients an increase in the thyrotropic hormone was detected leading to suspicion of the existence of associated primary hypothyroidism. Finally, several studies were carried out (basal measurements of cortisol and ACTH, stimulation with continual perfusion of ACTH, insulinic hypoglycemia, global study of adenohypophysary function, ACTH CRF release factor test, computerized tomography of the pituitary region) in both patients leading to the definitive diagnosis of isolated ACTH deficiency of idiopathic cause of possible pituitary origin without the existence of other associated hormonal deficiencies.     

Empty sella and headache

Empty sella is an anatomical condition caused by herniation of the subarachnoid space into the pituitary fossa through an incompetent sellar diaphragm. Headache seems to be one of the most frequently reported symptoms. We studied 13 headache patients (12 females, 1 male) presenting with primary empty sella (PES) on CT scan. The characteristics of the headache were analyzed and plasma levels of pituitary hormones or cortisol assessed. We confirmed the nonspecific nature of the headache in PES even though the majority of our patients complained of daily headache, mostly localized anteriorly. Hormone plasma levels were within normal range in all the patients assessed. However, four patients reported earlier endocrine disorders and more than half of the patients presented with obesity. In our opinion, PES should be suspected in middle-aged overweight women with daily headache even in the absence of endocrine symptomatology.     

MRI: incidence and evaluation of size and form criteria in hypophysis-healthy probands and in patients with detectable microadenomas

Magnetic resonance imaging (MRI) was performed in 42 patients with proven microadenomas and in 42 patients with normal pituitary hormone analysis. The normal MRI--anatomy of the pituitary gland and its possible variations with measurement of the volume and comparison of the anatomy with that of the gland after changes caused by microadenomas has to our knowledge not yet described. In this study we measured the height, coronary and sagittal diameter of the pituitary gland in both groups as well as other indirect signs of microadenomas (asymmetry of the gland, sella turcica, and the stalk). The pituitary volume indicates the expansion of microadenomas much better than the gland height (and the other diameters). Normal pituitary glands showed a significant lower volume (525 +/- 137 mm3 [R = 225-800 mm3]) than patients with proven microadenomas (734 +/- 393 mm3 [R = 335-2800 mm3], p < 0.001). The normal pituitary gland and sella turcica show a large variety of anatomic variations. These variations are less frequent in healthy subjects (10-21%) than in patients with microadenomas (48-71%). The described criteria are of some value in diagnosis of a suspected gland hypertrophy or microadenoma. In 75% of the patients with normal pituitary parameters and in 12% of the patients with microadenomas no indirect adenoma criteria was found in our study.     

Utility of magnetic resonance in the etiologic diagnosis of hypopituitarism

The diagnosis of hypothalamic-pituitary disorders relies on a combination of clinical and biochemical data and imaging techniques. During the last decade, computed tomography (CT) has been the best technique for the evaluation of the hypothalamuspituitary region, but in recent years magnetic resonance (MR) has improved the diagnostic efficiency of CT. We retrospectively review the clinical records of 40 hypopituitary patients from the endocrinology unit of our hospital. The aim of the present study was to establish the role of MR in the etiologic diagnosis and anatomic definition of hypopituitarism, when compared with CT. Secondarily, we studied the different pituitary hormones in this condition. The diagnoses were: 12 postsurgical hypopituitarism, 10 empty sella turcica, 7 Sheehan's syndrome, 5 idiopathic hypopituitarism, 3 pituitary disgenesis, 2 craniopharyngioma and 1 macroprolactinoma. GH was the most commonly affected hormone, followed by gonadotrophins, corticotrophin and thyrotrophin (100%, 94%, 76% and 68% respectively). In 24 patients both MR and CT studies were performed. MR was diagnostic in 22 patients, and CT in 15 patients (p < 0.05). MR offered improved diagnostic or anatomical data in 16 patients of the 24 in whom both techniques were performed (p < 0.05). We conclude that MR allows a better definition of the hypothalamus-pituitary region than CT, contributing to the etiologic diagnosis and improving the anatomical findings. Empty sella turcica should be considered a common cause of hypopituitarism.     

Doppler assessment of hemodynamic changes after hemodilution in retinal vein occlusion

Critical issues in diagnosis and treatment of pituitary disease are surveyed. The most relevant clinical aspects of hyperprolactinemia, acromegaly, Cushing's disease, secondary hyperthyroidism, syndrome of inappropriate ADH secretion, panhypopituitarism, growth hormone deficiency, gonadotropin deficiency, ACTH deficiency, TSH deficiency, and diabetes insipidus are discussed. Diagnostic and therapeutic issues in the approach to pituitary adenomas, craniopharyngiomas and pituitary apoplexy are analyzed.     

Clinical relapses and disease activity on magnetic resonance imaging associated with viral upper respiratory tract infections in multiple sclerosis

Inflammatory lesions of the hypophysis include lymphocytic hypophysitis, pituitary abscess, and granulomatous inflammation, with or without specific infections (i.e., sarcoidosis, mycobacteria). These lesions are known to mimic pituitary neoplasms. We report the clinical and pathologic findings in three patients who underwent transsphenoidal resection for presumed pituitary adenoma. Two were women aged 30 years (one with a 5-month history of headache, the other with a 1-year history of menstrual irregularity) and one was a 12-year-old girl with headache, nausea, and diabetes insipidus. Preoperative endocrinologic studies showed increased prolactin in one patient and normal serum thyroid stimulating hormone and prolactin levels in another. By magnetic resonance imaging (MRI), the first case had a 1.2-cm mass with increased signal on T1 and isointensity on T2, ring enhancement after gadolinium, and lateral deviation of the pituitary stalk. The second patient had a 1.1-cm "cystic" mass seen during magnetic resonance imaging with adjacent bony changes seen during computed tomography. In the third, computed tomography showed a hypodense pituitary mass that enlarged during 1-month observation. At surgery, abnormal soft tissue surrounded liquefied material in the anterior pituitary in all cases. Histologic studies showed fragments of intact normal anterior pituitary with preserved vascular and reticulin network and regions of anterior pituitary infiltrated by foamy histiocytes. Other fragments resembled granulation tissue, and some consisted of acellular debris. Histiocytes were immunoreactive for the macrophage marker CD68 and negative for S-100 and CD1a. Ultrastructurally, the normal adenohypophysis was permeated by lipid-laden macrophages. There were no well-formed granulomas or giant cells, hemosiderin, acid-fast bacilli, or fungi. Serial sections and keratin immunostains failed to identify an epithelial cyst lining or keratin among the debris. We propose the term "xanthomatous hypophysitis" for this lesion.     

Growth hormone deficiency and its treatment in adults

Deficiency of growth hormone produced in the pituitary is manifested not only in children by impaired growth but also in adults. It is encountered most frequently in adults after surgery or irradiation in the hypothalamo-pituitary area, less frequently in idiopathic disorders of growth hormone production and secretion, either isolated or in conjunction with other trophic pituitary hormones. The diagnosis of growth hormone deficiency must be assessed by dynamic stimulation tests: most frequently the insulin stimulation test is used. Growth hormone deficiency in adult age is manifested by various non-specific symptoms which resemble symptoms (manifestations) of ageing: increase of adipose tissue, deterioration of lipid metabolism, osteopenia, impaired cardiac output and others; the symptoms recede partly if growth hormone is administered for a prolonged period. Clinical trials which are under way should define not only suitable indications but also ways of administration of this expensive treatment.     

Prolactin-secreting pituitary carcinoma with implants in the cheek pouch and metastases to the ovaries. A case report and literature review

BACKGROUND: Prolactin-secreting pituitary carcinomas are uncommon, locally destructive neoplasms that rarely metastasize outside the central nervous system. The authors report a case of a prolactin-secreting tumor that initially presented as the empty sella syndrome. Two recurrences along transsphenoidal surgery tracts in cheek pouches were followed by distant metastases later in the abdomen and pelvis. Only 10 previous cases of either extracranial or intracranial metastases from prolactin-secreting pituitary carcinomas have been reported. No metastases below the diaphragm have been reported previously. METHODS: The patient's cheek pouch implants, lymph node metastases, ovarian metastases, and uterine metastases were studied with prolactin-specific immunohistochemistry. RESULTS: Long term treatment with bromocriptine, several debulking surgeries, extensive local radiation therapy (external beam and proton beam), and cytotoxic chemotherapy had little impact. Tamoxifen, however, may have slowed tumor growth. CONCLUSION: Tamoxifen may have efficacy in the treatment of prolactin-secreting pituitary carcinomas.     

Combined deficiency of thyroid stimulating hormone and growth hormone in a diabetic patient with Hashimoto thyroiditis

We report the case of a 36-year-old female patient with insulin dependent diabetes who developed hypothyroidism of pituitary origin after giving birth. She had low levels of free T4 and TSH with no response to i.v. TRH. Antimicrosome antibodies were increased (1/25000), suggesting Hashimoto's thyroiditis. The other hormones were normal except for a low level of growth hormone and insulin growth factor 1. There were no antibodies against the pituitary. MRI of the pituitary was normal. We suspect a vascular origin for this partial pituitary deficiency.     

Short stature and failure of pubertal development in thalassaemia major: evidence for hypothalamic neurosecretory dysfunction of growth hormone secretion and defective pituitary gonadotropin secretion

In patients with beta-thalassaemia major, frequent blood transfusions combined with desferrioxamine chelation therapy lead to an improved rate of survival. Endocrine disorders related to secondary haemosiderosis such as short stature, delayed puberty and hypogonadism are major problems in both adolescent and adult patients. A total of 32 patients with beta-thalassaemia major undergoing treatment at the Children's Hospital, University of G?ttingen were examined. Fourteen of these were short in stature. Growth hormone (GH) secretion was investigated in 13 patients exhibiting either a short stature or reduced growth rate. The stimulated GH secretion of 10 patients in this subgroup lay within the normal range. Studies of their spontaneous GH secretion during the night revealed that these patients had a markedly reduced mean GH and reduced amplitudes in their GH peaks. Low insulin-like growth factor (IGF)-I levels were seen in the growth-retarded thalassaemic patients. Eight were subjected to an IGF generation test and showed a strong increase in both IGF-I and insulin-like growth factor binding protein (IGFBP)-3 levels indicating intact IGF-I generation by the liver. Hypogonadotropic hypogonadism was found to be present in both the male and female patients with impaired sexual development. After priming with LH-releasing hormone (GnRH) per pump in 2 female and 5 male patients, no change in either their serum oestradiol or testosterone levels or in LH/FSH response to GnRH was observed suggesting that they were suffering from a severe pituitary gonadotropin insufficiency. Three male patients at the age of puberty but exhibiting short stature. low GH, low IGF-I and hypogonadism received low dose long-acting testosterone. After 3 12 months of therapy there was a marked growth spurt, higher nocturnal GH levels and an increase in both IGF-I and IGFBP-3. CONCLUSION: Reduced GH secretion and low IGF-I in thalassaemic patients are related to a neurosecretory dysfunction due to iron overload rather than to liver damage. Hypogonadotropic hypogonadism is caused by the selective loss of pituitary gonadotropin function. In patients with both GH deficiency and hypogonadism, low dose sexual steroid treatment should be considered either as an alternative or an additional treatment before starting GH therapy.     

Regulation of c-fos expression by EGF and GnRH in specific anterior pituitary cells from proestrous female rats

C-fos is an early expression oncogene that can be stimulated by a variety of regulators. It is expressed by subsets of all pituitary cells, with increased expression seen in proestrous rats. However, in freshly dispersed pituitary cells studied during different stages of the cycle, there is limited expression of fos by luteinizing hormone (LH) cells and little basal expression by cells with follicle-stimulating hormone (FSH) antigens. Proestrus is a time during which pituitary gonadotropes express peak levels of receptors for gonadotropin-releasing hormone (GnRH) and epidermal growth factor (EGF). We hypothesized that if GnRH or EGF stimulated fos activity in gonadotropes they would be most effective during the peak expression of their receptors. Anterior pituitaries were removed, cut into small pieces, and stimulated for 30 min. Total RNA was then collected and analyzed by Northern analysis. Both EGF and GnRH caused an increase in c-fos mRNA levels in the anterior pituitary gland compared with unstimulated pituitary glands assayed immediately after removal from the pituitary. However, the stimulatory effects were no greater than those seen with medium alone. This suggested that fos expression could be stimulated by local factors either in the pituitary or the medium itself. The second phase of the study focused on pituitary cells plated for 1 hr and then stimulated with EGF and GnRH for 15 min. Dual immunocytochemistry was done to learn which cell types expressed the fos proteins. After 15 min, EGF and GnRH both increased the percentages of fos-bearing cells above levels seen in medium alone. EGF stimulated fos proteins in subsets of FSH, adrenocorticotropin (ACTH), and growth hormone (GH) cells. GnRH increased fos proteins in subsets of ACTH and GH cells. These results suggest that EGF and GnRH may regulate fos expression, but not necessarily in gonadotropes. They also highlight the need for carefully timed experiments because endogenous factors in the pituitary itself may stimulate immediate early gene expression. (J Histochem Cytochem 46:935-943, 1998)     

A patient with acromegalic heart disease--a case report

A perioperative anesthetic management of a 69 year old woman with acromegaly whose clinical course was characterized by severe heart failure is described. The patient showed symptoms of massive cardiomegaly. Endocrine studies indicated that her pituitary tumor was active with hyperproduction of growth hormone. There was no demonstrable evidence for other known causes of heart disease. Following hormonal therapy using continuous subcutaneous infusion of somatostatin for about two months, there was improvement in daily activity and reduction in heart size. After the improvement of cardiac function, transsphenoidal hypophysectomy was performed under general anesthesia and its perioperative course was quite uneventful. We conclude that because cardiac involvement such as left ventricular dilatation in acromegaly might be reversible with proper treatment, any surgical procedure, as long as the case is elective, should be considered after hormone therapy.