A. Bizzarro

Detection of vasopressin cell antibodies in some patients with autoimmune endocrine diseases without overt diabetes insipidus

OBJECTIVE Cytoplasmic autoantibodies to vasopressin cells (AVP) have been detected in patients with idiopathic central diabetes insipidus and only in one patient with endocrine autoimmune diseases without clinical diabetes insipidus. The aim of this study was to look for AVP cell antibodies (AVP‐cell‐Ab) in human sera of a large population of autoimmune endocrine disease patients without diabetes insipidus and to test whether an occurrence of these antibodies in some patients can be associated with partial impairment of posterior pituitary function.

Association of Arginine Vasopressin-Secreting Cell, Steroid-Secreting Cell, Adrenal and Islet Cell Antibodies in a Patient Presenting with Central Diabetes insipidus, Empty Sella, Subclinical Adrenocortical Failure and Impaired Glucose Tolerance

A 36-year-old woman with central diabetes insipidus (DI), diagnosed when she was 7, was referred to our Endocrine Unit in January 1993 for further hormonal investigations. Clinical and laboratory findings confirmed the diagnosis of central DI. Cranial computed tomography and magnetic resonance imaging showed only an empty sella. Moreover, we noted impaired glucose tolerance and unusual findings of subclinical adrenocortical failure, i.e. high plasma renin activity with normal aldosterone levels, high ACTH despite normal basal and ACTH-stimulated cortisol levels. Immunological study of the patients serum showed the presence of arginine vasopressin (AVP)-secreting cell antibodies (Abs), steroid-producing cell Abs, adrenal and islet cell Abs. The following aspects of our case are stressed and discussed: (1) the presence of AVP-secreting cell Abs 29 years after the diagnosis of DI; (2) the association between DI, empty sella and subclinical autoimmune adrenocortical failure with unusual hormonal findings, and (3) impaired glucose tolerance with islet cell antibody positivity.

Pregnancy may favour the development of severe autoimmune central diabetes insipidus in women with vasopressin cell antibodies: description of two cases

Recently, an increased incidence of central diabetes insipidus (CDI) in pregnancy, and less frequently in the post partum period, has been reported, most probably favoured by some conditions occurring in pregnancy. This study was aimed at investigating the influence of pregnancy on a pre-existing potential/subclinical hypothalamic autoimmunity. We studied the longitudinal behaviour of arginine-vasopressin cell antibodies (AVPcAbs) and post-pituitary function in two young women with a positive history of autoimmune disease and presence of AVPcAbs, but without clinical CDI, and who became pregnant 5 and 7 months after our first observation. The behaviour of post-pituitary function and AVPcAbs (by immunofluorescence) was evaluated at baseline, during pregnancy and for 2 years after delivery. AVPcAbs, present at low/middle titres at baseline in both patients, showed a titre increase during pregnancy in one patient and after delivery in the other patient, with development of clinically overt CDI. Therapy with 1-deamino-8-d-arginine vasopressin (DDAVP) caused a prompt clinical remission. After a first unsuccessful attempt of withdrawal, the therapy was definitively stopped at the 6th and the 7th month of post partum period respectively, when AVPcAbs disappeared, accompanied by post-pituitary function recovery, persisting until the end of the follow-up. The determination of AVPcAbs is advisable in patients with autoimmune diseases planning their pregnancy, because they could be considered good predictive markers of gestational or post partum autoimmune CDI. The monitoring of AVPcAb titres and post-pituitary function during pregnancy in these patients may allow for an early diagnosis and an early replacement therapy, which could induce the disappearance of these antibodies with consequent complete remission of CDI.

Langerhans cell histiocytosis, diabetes insipidus, hyperprolactinemia and empty sella: A four-fold association. Report of two cases

Two cases of Langerhans cell histiocytosis (LCH) expressing as Hand-Schuller-Christian syndrome with diabetes insipidus, hyperprolactinemia and empty sella are here reported. Up-to-date this four-fold association is lacking in world literature and it is here discussed in the light if LCH is a cancer or the clinical expression of an immunologic disorder.

Soluble CD8 antigen, stimulated C-peptide and islet cell antibodies are predictors of insulin requirement in newly diagnosed patients with unclassifiable diabetes

To evaluate the predictive factors of insulin requirement in newly diagnosed patients with unclassifiable diabetes, 54 consecutive patients, aged less than 35 years, were prospectively followed for 3 years or more. At entry, haemoglobin HbAlc, basal and stimulated C-peptide concentrations, HLA phenotype, islet cell antibodies (ICA) status, and serum levels of soluble CD8 antigen (sCD8) were evaluated. After a median time of 9 (range 2–32) months, 31 patients (group 1) required insulin therapy, whereas 23 patients (group 2) remained non-insulin-requiring after 36 months. Group 1 patients were younger (P<0.05) and had higher HbAlc and sCD8 serum levels (P<0.001, respectively), a higher frequency of ICA positivity and of HLA DR3 and/or DR4 phenotype (P<0.005 andP<0.0001, respectively), and lower C-peptide concentrations (P<0.005 andP<0.0001, basal and stimulated, respectively) than group 2. The sensitivity, specificity, positive and negative predictive value, and overall accuracy for the subsequent insulin requirement were: sCD8 serum levels (>737 U/ml), 100%, 65%, 79%, 100% and 85%, respectively; stimulated C-peptide (<0.60 nmol/l), 71%, 96%, 96%, 74% and 81%, respectively; and ICA positivity (>20 JDFU), 45%, 91%, 87%, 55% and 65%, respectively. Thus, higher sCD8 serum levels, low stimulated C-peptide concentrations and ICA positivity are the most powerful predictors of subsequent recourse to insulin therapy in young, newly detected patients with unclassifiable diabetes.

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.

A new approach to the study of Graves’ ophthalmopathy: standardized A-scan echography and octreotide scintigraphy as possible parameters for disease activity

Eight patients, two male and six female, aged between 24 and 48 years, with Graves’ disease and severe ophthalmopathy were included in the study. A standardized A-scan echography was performed to evaluate the reflectivity of the extraocular muscles (EOMs); a planar scintigraphy (PS) and/or a single photon emission computed tomography (SPECT) were also performed at various times after endovenous injection of 111 MBq In-111 OCT, a somatostatin analogue.