Giuseppe Ruocco

Anti-hypothalamus and anti-pituitary antibodies may contribute to perpetuate the hypopituitarism in patients with Sheehan's syndrome.

OBJECTIVE While anti-pituitary antibodies (APAs) were detected in some patients with Sheehans syndrome (SS) suggesting an autoimmune pituitary involvement in the development of their hypopituitarism, hypothalamic cell anti-hypothalamus antibodies (AHAs) have not been investigated so far. DESIGN The aim of this study was to evaluate the presence of AHA and APA in SS patients to verify whether an autoimmune hypothalamic-pituitary process can contribute to their late hypopituitarism. METHODS Twenty women with SS with a duration of disease ranging from 3 to 40 years (median 25.5 years) were enrolled into the study. Out of 20 patients, 12 (60%) had panhypopituitarism and the others had partial hypopituitarism well corrected with appropriate replacement therapy. None of them had clinical central diabetes insipidus. AHA and APA were investigated by immunofluorescence method in all patients. In addition, a four-layer immunofluorescence method was used to verify whether AHA immunostained vasopressin-secreting cells (AVP-c) or not. RESULTS AHAs were found in 8 out of 20 (40%) and APAs in 7 out of 20 (35%) patients with titers ranging from 1:32 to 1:128 and 1:16 to 1:32 respectively; however, in none of these positive patients AHA immunostained vasopressin cells. None of controls resulted positive for both antibodies. CONCLUSIONS Patients with SS, even many years after the onset of SS, can show antibodies to pituitary and/or hypothalamic but not AVP-secreting cells. Antibodies to unknown hypothalamic cells (releasing factor-secreting cells) other than APAs suggest that an autoimmune process involving both the hypothalamus and pituitary gland may contribute to late pituitary dysfunction in SS patients.

Angiotensin converting enzyme inhibitors and reflux nephropathy: 2-year follow-up

Abstract We evaluated the effect of 2 years’ therapy with an angiotensin converting enzyme inhibitor (captopril) in 16 patients who had severe reflux nephropathy and microalbuminuria. During the period of therapy, microalbuminuria decreased, glomerular filtration rate measured by diethylenetriamine pentaacetate scan, serum creatinine, and blood pressure remained stable. We suggest the captopril was useful in reducing microalbuminuria and may have slowed the progression of renal damage in our patients.

Immunological and clinical aspects of lymphocytic hypophysitis

LYH (lymphocytic hypophysitis) is an autoimmune disease of the pituitary gland which can present with varying degrees of pituitary hormonal impairment and/or with symptoms related to pituitary enlargement. In this review, we provide an overview of the epidemiology, diagnosis, pathogenesis, treatment, and the role of organ-specific and antipituitary antibodies as potential markers of LYH. In addition, although the mechanisms underlying LYH are not completely understood, the role of prolactin, which plays an important part in maintaining immune system homoeostasis and is increased in the disease, is considered.

Antipituitary Antibodies in Idiopathic Hyperprolactinemic Patients

Abstract:  Hyperprolactinemia is often observed in lymphocytic hypophysitis (LYH). To clarify the possible autoimmune pituitary involvement in patients with apparently idiopathic hyperprolactinemia we investigated the presence of antipituitary antibodies (APA) in hyperprolactinemic patients with idiopathic hyperprolactinemia and in those with prolactinoma. Sixty‐six hyperprolactinemic patients (52 F, 14 M age range 28–42 years, group1) were studied. Of them, 34 out of 66 showed clinical features of hyperprolactinemia and subsequently underwent cabergoline therapy; the 32 out of 66 patients without symptoms of hyperprolactinemia did not receive cabergoline therapy. Moreover, 32 patients (24 F/8M, age range 23–44 years) with hyperprolactinemia due to microprolactinoma (group 2) were also studied. APA, by immunofluorescence method, and anterior pituitary function were evaluated in both groups of patients. APA were present in 17 out of 66 (25.7%) patients in group 1 with titers ranging from 1/16 to 1/64. All patients of group 2 were considered APA negative because these antibodies were found at low titer (≤1:4) only in five of them. With regard to the function of other pituitary hormones, all APA‐negative patients in group 1 and in group 2 showed a normal pituitary function; instead, a partial anterior pituitary impairment was observed in 6 out of 17 (35.3%) APA‐positive patients. In asymptomatic patients with apparently idiopathic hyperprolactinemia, APA detection could be useful to disclose forms of potential/subclinical stage of LYH. A future longitudinal study of these patients submitted to cabergoline therapy or free of therapy may be helpful to clarify this assumption.

Autoimmunity as a possible cause of growth hormone deficiency

A possible autoimmune aggression to pituitary somatotrophs has been suggested by the occurrence of antipituitary antibodies (APA) directed against GH-secreting cells in some cases of GH deficiency (GHD) both in adults and in children and in some patients with autoimmune poliendocrine syndrome. We also detected APA in some patients with idiopathic short stature (ISS) and suggested that the presence of these antibodies could identify those of them prone to develop GHD. In fact, patients with ISS, resulted positive for APA at the first observation, during a longitudinal follow-up showed an impaired GH response to the stimuli in subsequent years suggestive of acquired GHD. Also in such patients we demonstrated that the target of APA were the somatotrophs and that an autoimmune attack to these cells may be the underlying cause of hormonal impairment in several children with GHD positive for APA. In this connection we suggested that in these patients an early iso-hormonal therapy with recombinant GH may be useful to interrupt or delay the progression towards a clinical GHD.

Extraocular muscle antibodies and the occurrence of ophthalmopathy in Graves' disease.

objective  The aim of this study was twofold: first to investigate the presence of extraocular muscle antibodies (EMAb) in sera of Graves’ patients with ophthalmopathy characterized by clinical extraocular muscle (EM) involvement; second to evaluate in Graves’ patients without ophthalmopathy whether longitudinal variations of EMAb have a predictive role for the development of eye disease.

Anticorpi anti-ipofisi diretti contro le cellule GH-secernenti nei bambini con deficit idiopatico di GH e bambini con bassa statura idiopatica

RiassuntoNei pazienti con deficit idiopatico di GH dell’adulto (GHDI), il rilievo di anticorpi anti-ipofisi (Ab-I) diretti contro le cellule GH-secernenti può indicare la presenza di una patologia ipofisaria autoimmmune. Scopo dello studio è stato quello di 1) valutare la presenza di Ab-I in bambini prepuberi con deficit idiopatico di GH e in bambini con bassa statura idiopatica (BSI), identificando le cellule ipofisarie verso cui erano diretti gli anticorpi anti-ipofisi; 2) verificare se la presenza di Ab-I in bambini con BSI possa essere predittiva dello sviluppo di un deficit di GH (GHD). È stato pertanto eseguito uno studio cross-sectional e in parte longitudinale presso le Unità di Endocrinologia e Pediatria dell’Università di Napoli. Nello studio sono stati arruolati 26 bambini con GHDI (Gruppo 1), 60 bambini con BSI (Gruppo 2), 33 bambini con GHD dovuto a lesioni o anomalie ipotalamo-ipofisarie (Gruppo 3) e infine 40 soggetti di controllo. Diciannove bambini del Gruppo 2 sono stati rivalutati dopo 2 anni. Tutti i pazienti sono stati sottoposti a valutazione della secrezione del GH, alla determinazione dell’IGF-I sierico e degli Ab-I mediante immunofluorescenza indiretta. Al momento dell’arruolamento, Ab-I diretti contro le cellule GH-secernenti sono stati riscontrati in 7 bambini su 26 del Gruppo 1 e in 14 su 60 del Gruppo 2. Diciannove bambini, 8 con Ab-I positiv i e11 con Ab-I negativi, rivalutati 2 anni dopo l’arruolamento nello studio, mostravano lo stesso pattern anticorpale. La rivalutazione della secrezione del GH eseguita 2 anni dopo mostrava lo sviluppo di un GHD in tutti i pazienti con Ab-I positivi tranne uno, mentre nessuno dei pazienti con Ab-I negativi sviluppava GHD. In conclusione, il GHDI nei bambini può essere frequentemente associato con gli Ab-I diretti controllo le cellule GH-secernenti. Il riscontro di Ab-I in bambini con BSI potrebbe identificare coloro che sono predisposti a sviluppare il GHD.

Angiotensin Converting Enzyme Inhibitors and Reflux Nephropathy: 2-Year Follow-Up

We evaluated the effect of 2 years’ therapy with an angiotensin converting enzyme inhibitor (captopril) in 16 patients who had severe reflux nephropathy and microalbuminuria. During the period of therapy, microalbuminuria decreased, glomerular filtration rate measured by diethylenetriamine pentaacetate scan, serum creatinine, and blood pressure remained stable. We suggest the captopril was useful in reducing microalbuminuria and may have slowed the progression of renal damage in our patients.