Antipituitary Antibodies In Patients Research Articles

Antiadenohypophysis Autoantibodies in Patients with Nongluten‐related Gastroenteropathies

To investigate the presence of antipituitary antibodies (APA) in the serum of patients undergoing gastroenteropathies (GEP) other than celiac disease (CD). APA were analyzed in GEP patients (n= 103), CD patients (n= 94), idiopathic growth hormone (GH) deficiency patients (n= 21), and 98 age- and sex-matched controls. Indirect immunofluorescence was performed in cryostat sections of baboon pituitary gland. APA were detected in 30% of GEP patients, 38% of them showed failure to thrive. No significant differences were found when we compared thrive impairment in negative and positive APA GEP patients. Indeed, normal values of insulin-like growth factor 1 were found in 93% of positive APA GEP patients. APA were detected in 52% of the CD patients. Ninety-one percent of them, in contrast to GEP group, showed significant growth impairment (P < 0.05) when compared to APA negative CD individuals. GH-deficient non-CD patients did not show APA. We have shown the presence of APA in patients with nongluten-related enteropathies. The presence of antipituitary autoantibodies in GEP patients does not seem to be associated with failure to thrive as it occurs in CD.

Characterization of pituitary cells targeted by antipituitary antibodies in patients with isolated autoimmune diseases without pituitary insufficiency may help to foresee the kind of future hypopituitarism

Detection of antipituitary antibodies (APA) at high levels and with a particular immunofluorescence pattern in patients with autoimmune polyendocrine syndromes may indicate a possible future autoimmune pituitary involvement. This longitudinal study was aimed at characterizing in patients with a single organ-specific autoimmune disease the pituitary cells targeted by APA at start, verifying whether this characterization allows to foresee the kind of possible subsequent hypopituitarism. Thirty-six APA positive and 40 APA negative patients with isolated autoimmune diseases participated in the study. None of them had pituitary dysfunction at entry. Characterization by four-layer immunofluorescence of pituitary cells targeted by APA in APA positive patients at entry and study of pituitary function in all patients were performed every 6 months during a 5 year follow-up. Antipituitary antibodies immunostained selectively one type of pituitary-secreting cells in 21 patients (58.3 %, group 1), and several types of pituitary cells in the remaining 15 (41.7 %, group 2). All patients in group 1 showed subsequently a pituitary insufficiency, corresponding to the type of cells targeted by APA in 18 of them (85.7 %). Only 8 out of 15 patients in group 2 (53.3 %) showed a hypopituitarism, isolated in 7 and combined in the other one. None of APA negative patients showed hypopituitarism. The characterization of pituitary cells targeted by APA in patients with isolated autoimmune diseases, when the pituitary function is still normal, may help to foresee the kind of subsequent hypopituitarism, especially when APA immunostained selectively only one type of pituitary cells. A careful follow-up of pituitary function in these patients is advisable to allow an early diagnosis of hypopituitarism, even in subclinical phase and a consequent timely replacement therapy.

Prevalence of antipituitary antibodies in acromegaly

Acromegaly is a rare disorder due to an excessive production of growth hormone (GH), typically caused by a GH-secreting pituitary adenoma. Anti-pituitary antibodies (APAs) are often seen in patients with different kinds of pituitary pathologies. Because GH has been proposed as a possible antigen recognized by such antibodies, the prevalence of APAs may be higher in conditions characterized by excessive GH secretion. The primary aim of this study was to compare the prevalence of APAs in patients with acromegaly and in controls with other types of pituitary tumors and healthy subjects. Secondary aim was to characterize the pituitary cells targeted by the APAs. Thirty eight acromegaly patients and 215 controls, including 38 patients with prolactinomas, 64 with non-functioning pituitary adenomas (NFPA), and 113 healthy subjects were enrolled in the study. All subjects were tested for APAs using indirect immunofluorescence. Target cells recognized by APAs were identified by double staining immunofluorescence. APAs were significantly more prevalent in acromegaly cases than in healthy controls (10.5% vs. 1.8%, P < 0.05). This prevalence was similar to that found in patients with prolactinomas (7.9%) and NFPA (12.5%). Among APAs-positive subjects, antibodies recognizing somatotrope cells were more common in acromegaly cases than in healthy controls (3/4 vs. 0/113, P < 0.0001), but had similar frequencies in NFPA (2/8) and prolactinomas (1/3). APAs are more frequently found in patients with pituitary adenomas than healthy subjects, with no significant difference among the tumor types studied. GH-secreting cells could represent a target of the autoimmune response.

Prevalence and Functional Significance of Antipituitary Antibodies in Patients with Autoimmune and Non-Autoimmune Thyroid Diseases

Circulating antipituitary antibodies (APA) are markers of autoimmune hypophysitis, which may cause deficient pituitary function. The prevalence of APA in autoimmune thyroid disorders (AITD) is uncertain. The aims of this study were 1) to evaluate APA prevalence in a large series of patients with AITD and non-AITD and 2) to investigate the functional significance of APA by assessing pituitary function in APA-positive patients. We conducted a health survey on consecutive AITD and non-AITD patients at a tertiary referral center (Department of Endocrinology, Pisa). Subjects, including 1290 consecutive patients with thyroid disorders (961 AITD and 329 non-AITD) and 135 controls, were enrolled in the study. APA (indirect immunofluorescence), free T(4), free T(3), TSH, and organ-specific autoantibodies were assayed in all patients. Functional pituitary evaluation was performed in most APA-positive patients. APA frequency was higher in AITD (11.4%) than in non-AITD (0.9%; P < 0.0001) patients; all control subjects had negative APA tests. APA were more frequently found in Hashimoto's thyroiditis (13%) than in Graves' disease (7.1%; P = 0.05). Of 110 APA-positive AITD patients, 20 (18.2%) had autoimmune polyglandular syndrome, whereas 90 (81.8%) had apparently isolated AITD. APA positivity increased percentage of autoimmune polyglandular syndrome in our series from 10.4 to 13.5%. Of 110 APA-positive patients, 102 were submitted to dynamic testing for functional pituitary assessment; 36 patients (35.2%) had mild or severe GH deficiency (GHD). No additional anterior pituitary hormone deficiencies were found; one patient had central diabetes insipidus. Pituitary abnormalities at magnetic resonance imaging were found in most APA-positive GHD patients. APA are frequently present in patients with AITD. Patients should be tested for APA because positive tests are associated with GHD.

Growth hormone impaired secretion and antipituitary antibodies in patients with coeliac disease and poor catch-up growth after a long gluten-free diet period: a causal association?

Coeliac disease (CD) is usually associated with impaired growth in children. A gluten-free diet (GFD) induces a catch-up growth with the recovery of height in about 2 years. AIM AND DISCUSSION: The lack of the height improvement has been related to growth hormone (GH) secretion impairment. CD is an autoimmune disease often associated with other endocrine and non-endocrine autoimmune disease. The aim of this study was to evaluate antipituitary autoantibodies (APA) and antihypothalamus autoantibodies in CD children with poor clinical response to a GFD and growth hormone deficiency (GHD). We diagnosed CD on the basis of specific antibodies and endoscopic biopsies in 130 patients aged 1-15 years. Seven CD children, without catch-up growth after at least 12-months GFD, were tested for GH secretion and, in five out of seven patients, the diagnosis of GHD was made in the absence of metabolic and systemic diseases. APA and antihypothalamus antibodies were detected by the indirect immunofluorescence method in the seven CD children without catch-up growth factor and in 25 CD children without growth impairment matched for sex and age, and in 58 healthy children as control groups. APA resulted positive at high titres in four out of five CD-GHD patients and were also positive at low titres (<1:8) in three of only CD children and in two out of 58 controls. Hypothalamic-pituitary magnetic resonance imaging (MRI) was normal in all patients except in one with cystic pineal. APA have been previously detected not only in adults with GHD, but also in idiopathic GHD children, suggesting the occurrence of an autoimmune hypophysitis in these patients. In our study, the presence of APA in CD children without catch-up growth after GFD seems to be able to identify an autoimmune form of hypophysitis involving the somatotrophs cells.

Antipituitary Antibodies in Patients with Lymphocytic Hypophysitis

Background: Lymphocytic hypophysitis is one of the causes of hypopituitarism, which is considered an autoimmune reaction in the anterior pituitary. Method: We examined antipituitary antibodies in patients with lymphocytic hypophysitis and related diseases by immunoblotting method. Results: Autoantibodies to a 22-kDa human pituitary cytosolic protein were identified in significantly higher frequencies in sera from patients with lymphocytic hypophysitis (11 of 15, 73.3%) and isolated ACTH deficiency (7 of 9, 77.8%) compared with Hashimoto thyroiditis, Basedow’s disease and normal control subjects. Also, reactivity against a 49-kDa human pituitary cytosolic protein was seen in 6 of 15 patients (40%) with lymphocytic hypophysitis. N-terminal amino acid sequences of 22-kDa human and rat pituitary cytosolic protein were FPTIPLSVL and FPAMPLSSLFAN, respectively, suggesting that they are human and rat growth hormone, respectively. The pituitary dysfunction (at least one hormone dysfunction) was observed in 11 of 14 patients. Nine of them (82%) showed 22 kDa antibody but 2 of them (18%) did not. Conclusion: The present study demonstrated that pituitary autoantibodies could be involved in the pathogenesis of lymphocytic hypophysitis and could be a positive marker for the disease.

A Study of Anti-Pituitary-Antibodies in Patients with Hypopituitarism and Their Hereditary Background

Recently several types of anti-pituitary-antibodies (APA) have been found in patients with pituitary disorders including hypopituitarism and diabetes insipidus, and in postpartum women. However, the pathophysiological role(s) of APA still remains unknown. In order to elucidate the clinical significance of APA, longitudinal follow-up and family study of APA in patients with hypopituitarism were performed. APA in serum was examined in a total of 11 patients with various types of hypopituitarism (7 of isolated ACTH deficiency, 1 of partial hypopituitarism, 3 of Sheehan's syndrome, 6 males and 5 females). Chronic thyroiditis was associated in 3 out of 7 patients with isolated ACTH deficiency, and empty sella was found in each one patient with isolated ACTH deficiency and partial hypopituitarism, and in 3 patients with Sheehan's syndrome. APA was examined on 2 or 3 occasions at more than a 6 month interval (longitudinal study). In 5 patients, their 16 family members were examined for the presence of APA, and pituitary functions were evaluated in 3 out of 7 family members with positive APA (family study). For pituitary function tests, arginine infusion test, TRH, LH-RH or CRH test and insulin tolerance test were performed. APA reacting to rat pituitary cytoplasmic antigens (pituitary cell antibodies: PCA) and APA reacting to rat GH3 cells and/or mouse AtT20 cells surface antigens (pituitary cell surface antibodies: PCSA) were assayed with indirect immunofluorescence method. At the initial examination, 6 out of 11 patients (55%) showed positive APA. The patients were divided into 3 subgroups according to the longitudinal study: the group with disappearance of initially positive APA (3 patients), the group with altered titers or types of initially positive APA (3 patients), and the group with sustained initially negative APA (4 patients). No effects of replacement therapy on the alterations of APA were observed. In 16 family members of 5 patients (each 1 with partial hypopituitarism and isolated ACTH deficiency syndrome, and 3 with Sheehan's syndrome), APA in their sera were investigated. Seven out of 16 members (44%) showed positive APA. Among 6 first-degree relatives of 16 family members, both or either one of APA and PCSA were positive in 4 (67%). Out of 10 of their second- or third-degree relatives, 3 (30%) were positive for PCA or PCSA. All of 3 relatives with positive APA studied showed mild pituitary hypofunction without any clinical manifestations.(ABSTRACT TRUNCATED AT 400 WORDS)

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.