The primary empty sella syndrome : Analysis of the clinical characteristics,radiographic features,pituitary function and cerebrospinal fluid adenohypophysial hormone concentrations

Twelve cases of the primary empty sella syndrome were analyzed in regard to clinical findings, roentgenographic features, pituitary function and cerebrospinal fluid adenohypophysial hormone concentration. The findings were compared with those in 247 cases of the primary empty sella syndrome reviewed from the literature in order to determine the major characteristics of this disorder. The majority of patients are obese, multiparous women with normal pituitary reserve, normal visual fields and undetectable adenohypo-physial hormone concentrations in cerebrospinal fluid. In addition, occasional patients will have hypertension, pseudotumor cerebri and cerebrospinal fluid rhinorrhea. Patients who present with the typical features of the primary empty sella syndrome should be evaluated periodically with pituitary function testing, visual field examinations and cerebrospinal fluid adenohypophysial hormone determinations. If these parameters remain normal during careful follow-up studies, the patient is likely to have an empty sella, and pneumoencephalographic and angiographic studies can be avoided.     

ACTH deficiency and TSH hypersecretion in a patient with empty sella turcica

In a 49-year-old woman with empty sella syndrome, corticotropin (ACTH) deficiency and various abnormalities, including increased thyrotropin (TSH) secretion, growth hormone (GH) deficiency, and inappropriately high insulin with early phase hypoglycemia, during an oral glucose tolerance test were found. Existence of serum antipituitary antibody suggested that the empty sella and ACTH deficiency may be caused by an autoimmune destruction of the pituitary gland. All of the accompanying abnormalities except for increased TSH secretion were corrected with glucocorticoid supplement. Thyroidal responses to an increase and decrease of endogenous TSH were qualitatively normal, indicating that the patient's TSH was biologically active and the set point of hypothalamic-pituitary feedback regulation for TSH secretion was shifted.     

Thyrotropin and prolactin pituitary reserve in the "empty sella syndrome".

Ten patients (8 women, 2 men) with the "empty sella syndrome" were studied to evaluate the pituitary reserve of human thyrotropin (hTSH) and prolactin (hPRL). None of the patients had signs or symptoms of hypopituitarism or primary hypothyroidism. All patients had normal baseline thyroid function tests except for 2 patients with mild elevations in total triiodothyronine as measured by competitive protein displacement assay (T3D). Eight of ten patients had normal hTSH responses to thyrotropin releasing hormone (TRH), whereas the 2 patients with elevated T3D had blunted TRH responses. In the 4 patients studied, the metabolic clearance (MCR) and production rates (PR) of hTSH were normal. In 9 of 10 patients normal baseline serum hPRL levels were detected, and each responded to TRH. In one case serum hPRL was undetectable and failed to respond to TRH. The assessment of other anterior pituitary function revealed few minor abnormalities. In summary, like other anterior pituitary hormones, the pituitary reserve in "empty sella syndrome" of hTSH and hPRL is usually normal. When abnormalities do occur, they are attributable to other co-existent endocrine pathology.     

Primary empty sella syndrome, ACTH hypersecretion, and normal adrenocortical function. Report of two cases

Although the primary empty sella syndrome (PESS) is associated with normal endocrine function or subtle pituitary insufficiency, pituitary hormone hypersecretion associated with PESS has also been recognized. ACTH hypersecretion and primary empty sella syndrome have previously been reported in patients with either Cushing's disease or Addison's disease. This report describes two unique patients with ACTH hypersecretion, primary empty sella syndrome, and normal cortisol dynamics. The investigators speculate that this association may have resulted from infarction of hyperplastic adenohypophyseal corticotrophes due to production of an ACTH peptide with reduced biologic activity. These two cases emphasize that primary empty sella syndrome may be associated with ACTH hypersecretion and normal adrenocortical function.     

Delayed recovery of thyrotropin responsiveness after radioactive iodine therapy for hyperthyroidism

BACKGROUND: After radioactive iodine therapy for hyperthyroidism, an expected lag in the responsiveness of thyrotropin (TSH) is 60 to 90 days. In our experience, however, many patients seemed to have a more prolonged lag in TSH recovery. METHODS: A retrospective chart review was performed in 58 patients who underwent radioactive iodine therapy for hyperthyroidism (52 with Graves disease, 5 with toxic nodular goiters, and 1 with a toxic adenoma). RESULTS: Forty-nine patients (84%) had appropriate responses of TSH for their level of serum thyroid hormone. Thirty-one became hypothyroid, 12 became euthyroid, and 6 remained hyperthyroid. Nine patients (16%) had a lag in their TSH responsiveness. The TSH remained low for 3 months in 5 patients, for 9 months in 3 patients, and 1 patient had low levels of serum TSH for at least 12 months. CONCLUSIONS: After radioactive iodine therapy for hyperthyroidism, decisions upon further therapy must be based upon the clinical status as well as the serum levels of TSH and thyroid hormones.     

Hyperthyroidism due to a thyrotropin-secreting pituitary adenoma. Studies of thyrotropin and subunit secretion

A 58-year-old man had symptoms of hyperthyroidism and congestive heart failure. While hyperthyroid, his serum thyrotropin (TSH) level was inappropriately elevated at 6.1 microunits/mL. The molar ratio of alpha subunit to TSH was 2.5, suggesting the presence of a TSH-secreting pituitary tumor. Further evaluation disclosed an enlarged sella turcica with posterior erosion, and an intrasellar mass was visualized on computed tomographic scan. Neither serum TSH nor alpha subunit levels became elevated after administration of thyrotropin-releasing hormone, nor were they suppressed by a dopamine infusion. Serum TSH but not alpha subunit levels rose during antithyroid drug therapy. Estrogens produced a partial reduction in serum alpha subunit concentration (presumably reflecting the nontumorous gonadotroph contribution to circulating alpha subunit). Dexamethasone completely suppressed serum TSH level but had no effect on the alpha subunit level, suggesting a differential feedback of glucocorticoids on TSH and alpha secretion. The patient was treated with pituitary irradiation rather than surgery because of his underlying heart disease.     

COEXISTING PRIMARY EMPTY SELLA SYNDROME AND ACROMEGALY*

SUMMARY The‘empty’sella syndrome is now a more frequent diagnosis due to the increased use of pneumoencephalography in the evaluation of the enlarged pituitary fossa. This syndrome has also been classified into a‘primary’form in which there has been no prior pituitary irradiation or surgery, and a ‘secondary’ form in which the empty sella is found after such procedures. Most patients with the primary empty sella syndrome are found to have normal pituitary function while about 30% have varying degrees of hypopituitarism (Neelon et al., 1973). It is not widely appreciated, however, that the primary empty sella may harbour a pituitary tumour with resultant acromegaly. In this report we describe two such patients who presented with active acromegaly. This entity of pituitary tumour in a primary empty sella merits careful consideration since the coexistence of these two findings may influence the therapeutic approach that might otherwise be appropriate for the pituitary tumour.     

Recombinant human thyrotropin in thyroid cancer and hypopituitarism due to sella metastasis.

We present a patient with thyroid cancer and hypopituitarism who required recombinant human thyrotropin (rhTSH) for 131I scanning with respect to subsequent therapy. The thyroid cancer had been unknown until central neurological symptoms developed, leading to the diagnosis of a huge metastasis to the sella that was the only manifestation of metastatic spread. The failure to generate endogenous thyrotropin (TSH) was overcome by the use of rhTSH for performing a 131I test. Unfortunately, the 131I uptake was not sufficient for therapy. This subject is the first reported case who required the application of rhTSH due to a single thyroid cancer metastasis in the sella region with secondary failure to generate endogenous TSH.     

Cushing's syndrome in a patient with an empty sella turcica and a microadenoma of the adenohypophysis

A patient with Cushing's syndrome and an empty sella turcica is presented. A pituitary microadenoma was removed by the transsphenoidal approach. The Cushing's syndrome was alleviated, and the function of the other pituitary trophic hormones has remained normal eight months after surgery. It is emphasized that an empty sella turcica does not rule out a pituitary tumor. The therapeutic implications are discussed.     

Hyperthyroidism due to inappropriate secretion of thyrotropin in 10 patients.

PURPOSE: The syndrome of inappropriate thyroid-stimulating hormone (TSH) secretion, characterized by elevated serum free thyroxine and triiodothyronine levels in association with measurable serum TSH concentrations, remains an uncommon cause of hyperthyroidism that is being recognized with increasing frequency. The hyperthyroidism may be due to either neoplastic pituitary TSH secretion or selective pituitary resistance to thyroid hormone. In an effort to better understand this rare cause of hyperthyroidism, we undertook a retrospective analysis of our institution's experience with this condition. PATIENTS: We reviewed our cumulative experience (10 patients) with hyperthyroidism due to the syndrome of inappropriate secretion of TSH. RESULTS: Six patients were diagnosed with TSH-secreting pituitary adenomas and four were found to have selective pituitary resistance to thyroid hormone. One patient with tumor had a TSH-secreting pituitary adenoma in the setting of multiple endocrine neoplasia syndrome. In all patients with tumor, hyperthyroidism was successfully treated with transsphenoidal adenomectomy with or without pituitary radiotherapy. All four patients with pituitary resistance had thyroid ablation or resection prior to their correct diagnosis. Therefore, therapy for this group of patients involved thyroid hormone replacement and efforts to suppress TSH hypersecretion. All 10 patients have done well clinically, with follow-up ranging from 2 weeks to 13 years. CONCLUSIONS: Adequate treatment exists for the two primary causes of TSH hypersecretion. TSH-secreting pituitary adenomas are treated with surgery and, if necessary, adjuvant pituitary radiotherapy. The results are generally good if the tumor is diagnosed and treated at an early stage. Primary therapy for hyperthyroidism due to selective pituitary resistance to thyroid hormone is aimed at suppression of pituitary TSH hypersecretion. The evaluation of any patient with hyperthyroidism must be thorough and, in some cases, should include measurement of TSH to determine the presence of inappropriate secretion. Eliminating this diagnosis will help avoid improper and potentially harmful treatment of hyperthyroid patients.     

Diagnosis and evaluation of patients with an enlarged sella turcica

A prospective analysis of the roentgenographic and laboratory parameters in 100 patients with an enlarged sella turcica was made. Seventy-five patients had no visual symptoms: 27 had primary intrasellar tumor; 25 had the empty sella syndrome; 13 had an extrasellar process; and in 10, no final diagnosis was made because air study was omitted. However, these patients remained asymptomatic for up to three years. Eighteen of the patients with a primary intrasellar tumor had symptomatic pituitary dysfunction; nine were asymptomatic. Five of 14 patients studied had elevated plasma prolactin levels. Of the 25 patients with the empty sella syndrome and the 10 patients in whom no final diagnosis was made, none had any clinical endocrine or visual abnormalities, although in 10 of these 35 patients, results of laboratory studies were compatible with pituitary dysfunction. In these cases, air study was necessary to differentiate a clinically silent pituitary tumor from the empty sella syndrome. This emphasizes the high incidence of the empty sella syndrome in patients with enlarged sella, and also confirms the high incidence of hyperprolactinemia in patients with pituitary tumors.     

AUTOIMMUNE POLYGLANDULAR SYNDROME, PRIMARY EMPTY SELLA, AND ACUTE LYMPHOCYTIC LEUKAEMIA

A young man is reported with an autoimmune polyglandular syndrome (APS) characterized by Addison's disease, primary hypothyroidism, primary hypogonadism, vitiligo, associated with primary empty sella and partial impairment of pituitary hormone secretion. Two years later the patient showed a null cell type acute lymphocytic leukaemia, immediately after surgery for an inguinal hernia. Pathogenetic mechanisms are postulated on the basis of HLA studies and lymphocytic typing.     

Effects of amiodarone and desethylamiodarone on pituitary deiodinase activity and thyrotropin secretion in the rat

The effect of acute administration of amiodarone, its major metabolite desethylamiodarone and iodine in an amount equal to that contained in amiodarone on serum thyroid hormone and thyrotropin (TSH) concentrations and hepatic and pituitary 5' deiodination of thyroxine (T4) in the euthyroid and hypothyroid rat was evaluated. Amiodarone, desethylamiodarone and iodine all caused a decrease in serum T4 and triiodothyronine (T3) concentrations in euthyroid rats, while serum TSH concentrations and pituitary and hepatic 5' deiodinase activities were decreased only in the amiodarone and desethylamiodarone-treated animals. Serum TSH was increased in the iodine treated rats. Amiodarone, but not iodine, decreased serum T3 and TSH concentrations and pituitary and hepatic 5' deiodinase activities in hypothyroid rats. Inhibition of hepatic 5' deiodinase activity was also observed by the addition of amiodarone in vitro in the absence of dithiothreitol (DTT) but not in the presence of DTT. The decrease in the serum T4 concentration observed with amiodarone and desethylamiodarone administration is probably secondary to the inhibitory effect of iodine released from the drugs on thyroidal T4 synthesis and secretion. Iodine inhibition of thyroidal T3 synthesis and secretion, decreased T4 substrate for a peripheral generation of T3 and inhibition of T4 to T3 conversion all contribute to the decrease in serum T3 observed. The decrease in the serum TSH concentration, despite low serum T4 and T3 concentrations and inhibition of pituitary 5' deiodinase, suggest that amiodarone may function as a thyroid hormone agonist in the pituitary.(ABSTRACT TRUNCATED AT 250 WORDS)     

Empty sella of normal size in Sheehan's syndrome

This report describes the findings of computed tomography of the sella turcica region in 13 women in whom postpartum hypopltuitarism developed in the absence of a pituitary tumor. Seven patients had the typical history of severe postpartum hemorrhage (Sheehan's syndrome). Computed tomographic scanning in these patients revealed absence (in six patients) or marked reduction (in one patient) of the amount of demonstrable pituitary tissue. The pituitary fossa was occupied by material with the density of cerebrospinal fluid, resulting in the appearance of an “empty sella.” Sella size was within the normal range in six of the seven patients and enlarged in one. The six remaining patients lacked a characteristic history of vascular collapse, although several did have postpartum complications. The radiologic findings in four of these patients were similar to those seen in the patients with typical Sheehan's syndrome: one patient had a partially empty sella and another had normal results of computed tomographic scanning. Thus, 11 of 13 women with postpartum hypopituitarism were noted to have an empty or partially empty sella of normal size. This report represents the first radiologic documentation of Sheehan's syndrome as a cause of the secondary empty sella, with the characteristic finding being an empty sella of normal size.     

The empty sella: results of treatment in 76 successive cases and high frequency of endocrine and neurological disturbances

OBJECTIVE: We assessed the frequency of endocrine or neurological disturbances and the results of surgery in patients with empty sella, diagnosed with cisternography and/or computerized tomography scanning. DESIGN AND PATIENTS: Analysis of hospital records of 76 successive patients (73 primary, three secondary empty sella) from a single institution. MEASUREMENTS: Clinical and neuro-ophthalmological evaluation. Serum PRL, GH, TSH, LH, FSH, T4, T3 by radioimmunoassay. Diagnosis of empty sella with cisternography and/or computerized tomography scanning (n = 69), or discovered at surgery (n = 7). RESULTS: Patients with empty sella had: headache (69.7%), visual disturbances (34.2%), cerebrospinal fluid rhinorrhoea (11.8%), endocrine disturbances (51.4%, including hyperprolactinaemia, acromegaly, Cushing's syndrome). A pituitary tumour was discovered in two patients, in seven other ones it was suspected but not found at surgery. Transsphenoidal packing of empty sellas was done in 56 cases, with 7.1% post-operative complications. With surgery there was improvement of headache in 71%, of visual disturbances in 46%. Cerebrospinal fluid rhinorrhoea (discovered at surgery in four other patients) was not resolved by the first operation in six out of 13 patients. In 20 patients without surgery, headache improved in 64.6%. CONCLUSIONS: The empty sella is frequently associated with a variety of neurological and endocrine disturbances, which is contrary to conventional belief. Cerebrospinal fluid rhinorrhoea is not a rare complication and it may be difficult to treat. Some cases of empty sella may be due to partial pituitary apoplexy. Autoimmunity may have existed in other cases. Surgery may be useful in many patients, but a judicious selection is needed because it entails complications and non-operated patients may improve spontaneously.     

Empty sella resulting from the spontaneous resolution of a pituitary macroadenoma.

Recent studies suggest that the infarction of a pituitary adenoma may be a frequent cause of an empty sella turcica. However, to date, evidence of such progression has been largely speculative. We present the case of a patient with a pituitary macroadenoma that underwent spontaneous involution resulting in an empty sella, as documented by serial magnetic resonance imaging scans. A brief review of the proposed causes of primary empty sella, with emphasis on pituitary necrosis, is provided.     

Antipituitary antibodies in patients with the primary empty sella syndrome

The frequency of detection of serum antibodies against pituitary cells was determined in 32 patients with the primary empty sella syndrome. Antibodies reacting with corticotropin-secreting mouse AtT20 and PRL-secreting rat GH3 cells were found in 24 (75%) and 15 (47%), respectively, of the 32 patients; 14 patients (44%) had antibodies reacting with both cell lines. In patients with pituitary adenomas, the prevalence of antipituitary antibodies was significantly lower than in those with the empty sella syndrome; 1 of 9 acromegalic patients had antibodies reacting with GH3 cells, and 2 of 9 prolactinoma patients and 1 of 7 patients with nonfunctioning adenomas had antibodies reacting with both AtT20 and GH3 cells. Among 6 patients with idiopathic diabetes insipidus, 1 patient had antibodies reacting with AtT20 and GH3 cells, and 2 patients had antibodies reacting with either AtT20 or GH3 cells. None of 5 patients with established autoimmune diseases (3 with systemic lupus erythematosus and 2 with autoimmune adrenal failure) had antipituitary antibodies in their serum. These results suggest that pituitary antibodies may be related to the development of pituitary atrophy and the primary empty sella syndrome, and that the test may be clinically useful as a screening test for the empty sella syndrome.     

Presence of anti-pituitary hormone antibodies in patients with empty sella syndrome and pituitary tumours*

OBJECTIVE We evaluated the presence of anti-pituitary hormone autoantibodies (APHA) in patients with primary empty sella syndrome and pituitary tumours and examined the correlation of positive antibodies with the hormonal deficiencies. DESIGN Case-control, retrospective study. PATIENTS Eleven patients were identified with primary empty sella syndrome or a pituitary tumour by magnetic resonance imaging or computed tomography scanning. Six healthy, normal subjects without evidence of a pituitary problem served as the control group. MEASUREMENTS Anti-pituitary hormone autoantibodies against purified pituitary hormones were measured in ail subjects utilizing an immunoblotting technique. All patients with pituitary disease had their medical records reviewed for any hormonal evaluation. RESULTS All of the normal subjects were negative for antipituitary hormone antibodies. Forty-five per cent of patients with pituitary disease (pituitary tumours or primary empty sella syndrome) had positive antipituitary hormone antibodies. Of the five patients with positive antipituitary hormone antibodies, anti-ACTH antibodies were the most common (5/5) followed by anti-TSH and anti-GH antibodies (2/5 for each). The hormonal deficiencies failed to correspond with the antipituitary hormone antibodies. Anti-ACTH antibody had a sensitivity of 50% with a specificity of 56%. The anti-TSH antibody yielded a sensitivity of 67% with a specificity of 100%. The anti-FSH/ LH antibody reported a 0% sensitivity. CONCLUSIONS Detection of antipituitary hormone antibody was unable to discriminate between empty sella syndrome and pituitary tumours. The presence of these antipituitary hormone antibodies were neither specific for, nor predictive of, the endocrine deficiencies.     

Empty sella syndrome associated with diabetes insipidus: case report and review of the literature

Alteration of posterior pituitary function in the empty sella syndrome is rare. A case of central diabetes insipidus and clear-cut deficiency of gonadotropins associated with an empty sella is described. Although computed tomographic scan revealed a defect of the diaphragma sellae, other pathogenic mechanisms are considered. Previously documented cases of empty sella syndrome associated with diabetes insipidus are reviewed.     

Primary empty sella syndrome with visual field defects

A patient with an enlarged, asymmetric sella turcica and visual field defects suggestive of a pituitary or parasellar tumor underwent extensive roentgenographic and pituitary function studies. No abnormalities in pituitary luteinizing hormone, follicle-stimulating hormone, thyroid-stimulating hormone, ACTH, prolactin or vasopressin secretion were detected. Growth hormone secretion was provoked by arginine infusion but not by hypoglycemia. Pneumoencephalography revealed air in the sella turcica, and no evidence of tumor. Thus, an enlarged sella turcica in a patient with visual field defects but normal pituitary function may suggest the presence of an “empty sella syndrome.”