Pituitary autoimmunity: 30 years later

Abstract

Pituitary autoimmunity encompasses a spectrum of conditions ranging from histologically proven forms of lymphocytic hypophysitis to the presence of pituitary antibodies in apparently healthy subjects. Hypophysitis is a rare but increasingly recognized disorder that typically presents as a mass in the sella turcica. It mimics clinically and radiologically other non-secreting sellar masses, such as the more common pituitary adenoma. Hypophysitis shows a striking temporal association with pregnancy, and it has been recently described during immunotherapies that block CTLA-4. Several candidate pituitary autoantigens have been described in the last decade, although none has proven useful as a diagnostic tool. This review summarizes the advances made in the field since the publication of the first review on pituitary autoimmunity, and the challenges that await clarification.

Longitudinal behavior of autoimmune GH deficiency: from childhood to transition age

“…Instead, the persisting detection of APA accompanied by impairment of pituitary function in the other 12 patients (75%), in whom APA to somatotrophs had been detected at high titer at diagnosis, seems to indicate that a remission of pituitary autoimmunity in transition period may not occur when the pituitary immune process was very active in childhood age. Thus, our results on the other hand confirm the usefulness of searching for APA in patients with GHD in order to disclose those with pituitary autoimmunity, as also demonstrated by other authors (8,9,18,19,22,23), on the other hand seem to indicate that the titer level of these antibodies at diagnosis may help to foresee the possible future evolution of the pituitary autoimmune process. Another interesting point emerging from our results concerns the relationship evidenced at the observation in transition period between the detection of the type of pituitary hormone-secreting cells immunostained by APA and the kind of pituitary hormone deficiency in the 12 patients with persistence of pituitary autoimmunity in this period.…”

“…This is the first evidence in patients with autoimmune GHD, diagnosed in childhood and treated with rGH replacement therapy until the transition age, of a shift of APA from a pituitary target at diagnosis (somatotrophs) to another pituitary target (gonadotrophs) at the observation in transition period, with consequent variation of the selective kind of hypopituitarism, from GHD to HH. The cause of this surprising behavior is at present unknown, perhaps because the true pituitary antigen(s) responsible for the autoimmune response have yet to be identified, despite several factors being suggested as possible autoantigens (22,23,24,25,26,27,28).…”

Nivolumab-induced hypophysitis in a patient with advanced malignant melanoma

“…These clinical characteristics of ipilimumab-induced hypophysitis differ from those of idiopathic AH, which has a higher incidence among younger females and sometimes cause diabetes insipidus and visual disturbances due to the compression of the optic chiasm by the enlarged pituitary gland and stalk [1]. Idiopathic isolated ACTH deficiency may be caused by AH, as evidenced by the pathological demonstration of lymphocyte infiltration in the anterior pituitary gland, an association with autoimmune diseases in other organs such as Hashimoto's thyroiditis, vitiligo, and premature ovarian failure, and the presence of anti-pituitary antibodies [1,14,15]. In hypophysitis induced by immune-checkpoint inhibitors, enhanced immune responses have also been suggested to play pathological roles [8,[10][11][12].…”

“…ACTH-deficient patients, were also negative [14,15]. Although invasive pituitary biopsy was not performed on the advanced cancer patient from an ethical view point, we clinically excluded other potential causes of the pituitary/stalk enlargement such as IgG4-related diseases, sarcoidosis, or malignant lymphoma by measuring immunological markers specific for the individual diseases (Table 2).…”

Autoimmune hypophysitis: a study of natural course

“…1,2 The reported incidence of autoimmune hypophysitis is one in nine million. 3 A recent study reported an estimated incidence of autoimmune hypophysitis in India as 2.4 per ten million population. 4 Increasing recognition of the disease is contributing for the recent increase in the incidence.…”