IgG4-related disease (IgG4-RD) is an immune-mediated fibro-inflammatory condition which can affect various organs including the pituitary gland. The true annual incidence of this condition remains widely unknown. In addition, it is unclear whether IgG4 antibodies are causative or the end result of a trigger. With no specific biomarkers available, the diagnosis of IgG4-related hypophysitis remains a challenge. Additionally, there is a wide differential diagnosis. We report a case of biopsy-proven IgG4-related hypophysitis in a young man with type 2 diabetes mellitus.
IgG4-related hypophysitis is part of a spectrum of IgG4-related diseases.
Clinical manifestations result from anterior pituitary hormone deficiencies with or without diabetes insipidus, which can be temporary or permanent.
A combination of clinical, radiological, serological and histological evidence with careful interpretation is required to make the diagnosis.
Tissue biopsy remains the gold standard investigation.
Disease monitoring and long-term management of this condition is a challenge as relapses occur frequently.
IgG4-related hypophysitis is an important diagnostic consideration in patients with a pituitary mass or pituitary dysfunction and can initially present with headaches, visual field deficits and/or endocrine dysfunction. Isolated IgG4-related pituitary disease is rare, with most cases of IgG4-related disease involving additional organ systems. We report the case of a teenage female patient with isolated IgG4-related hypophysitis, diagnosed after initially presenting with headaches. Our patient had no presenting endocrinologic abnormalities. She was treated with surgical resection, prednisolone and rituximab with no further progression of disease and sustained normal endocrine function. This case, the youngest described patient with isolated IgG4-related hypophysitis and uniquely lacking endocrinologic abnormalities, adds to the limited reports of isolated pituitary disease. The use of rituximab for isolated pituitary disease has never been described. While IgG4-related hypophysitis has been increasingly recognized, substantial evidence concerning the appropriate treatment and follow-up of these patients is largely lacking.
IgG4-related hypophysitis most often occurs in the setting of additional organ involvement but can be an isolated finding. This diagnosis should therefore be considered in a patient presenting with pituitary abnormalities.
Most patients with IgG4-related hypophysitis will have abnormal pituitary function, but normal functioning does not exclude this diagnosis.
Corticosteroids have been the mainstay of therapy for IgG4-related disease, with other immunosuppressive regimens being reserved for refractory cases. Further research is needed to understand the effectiveness of corticosteroid-sparing regimens and whether there is utility in using these agents as first-line therapies.
A 76-year-old man had a hypopituitarism including adrenal insufficiency, hypogonadism and hypothyroidism. Based on various findings including the swelling of the pituitary gland, increase of serum IgG4 level and abundant IgG4-positive plasma cell infiltration in immunostaining of the pituitary gland, we diagnosed this subject as IgG4-related hypophysitis. In general, a high-dose glucocorticoid treatment is effective for IgG4-related disease. His clinical symptom, laboratory data and adrenal insufficiency were almost improved without any therapy. The serum IgG4 level was decreased and pituitary size was normalized with hydrocortisone as physiological replacement. This case report provides the possibility that IgG4 level is decreased spontaneously or with physiological dose of glucocorticoid therapy.
We performed the pituitary gland biopsy and histochemical examination glucocorticoid therapy in a subject with IgG4-related hypophysitis.
This case report provides the possibility that IgG4 level is decreased spontaneously or with a physiological dose of glucocorticoid therapy. We reported the clinical course of IgG4-related hypophysitis without a high-dose glucocorticoid treatment, although there were a few reports about the retrospective examination.
Although the patient had still higher IgG4 level compared to normal range, his clinical symptom disappeared and his laboratory data were improved.
We should keep in mind the possibility of IgG4-related hypophysitis when we examine one of the uncertain causes of a hypopituitarism including adrenal insufficiency, hypogonadism and hypothyroidism.
IgG4-related disease (IgG4-RD) is a rare but increasingly recognised condition, emerging as a clinical entity following the observation of the associations of autoimmune pancreatitis. IgG4-RD is characterised by extensive infiltration of IgG4-positive plasma cells into multiple organs and raised serum IgG4 levels. Clinical manifestations of IgG4 disease classically include autoimmune pancreatitis, lacrimal or salivary gland infiltration (formerly known as Mikulicz disease) and retroperitoneal fibrosis. More rarely, IgG4 disease can cause pituitary hypophysitis. Although most frequently described in middle-aged males, the epidemiology and pathogenesis of the disease remain largely undefined. Nevertheless, an understanding of the wide variety of clinical manifestations of this multi-system condition is undeniably important given the often excellent outcomes following treatment. We describe an unusual presentation of IgG4 disease with isolated diabetes insipidus secondary to pituitary hypophysitis. The patient in question subsequently developed chest pain secondary to mediastinal lymphadenopathy and tubulo-interstitial nephritis leading to renal dysfunction. He was successfully treated with oral steroids and had regular follow-up, and remains well at follow-up 2 years later.
IgG4 disease, although rare, is increasing in prevalence largely due to increased recognition of its clinical manifestations, including autoimmune pancreatitis, lacrimal or salivary gland infiltration, retroperitoneal fibrosis and, more rarely, lymphocytic hypophysitis presenting as diabetes insipidus.
IgG4 disease is highly treatable, and symptoms may show complete resolution with administration of steroids, highlighting the importance of correct and timely diagnosis.
Causes of lymphocytic hypophysitis are varied and not distinguishable radiologically. Given the difficulty in biopsying the pituitary, careful attention must be paid to the systemic clinical presentation to provide clues as to the underlying disorder.
Hiroto MinaminoThe First Department of Medicine, Wakayama Medical University, 811-1, Kimiidera, Wakayama, 641-8509, Japan Department of Diabetes and Endocrinology, Wakayama Red Cross Hospital, Wakayama, Japan
A 73-year-old man with Hashimoto's thyroiditis (HT) suffered from purpura on the lower legs. He was diagnosed with IgG4-related disease (IgG4-RD) with serum IgG4 elevation and dacryo-sialadenitis confirmed histologically. Serum Th2 and Treg cytokines, interleukin 7 (IL7), IL8 and Th2 chemokine levels were elevated, while skewed Th1 balance was seen in fluorescence-activated cell sorting (FACS). Therefore, preferential Th1 balance in HT appeared to be followed by IgG4-RD characterized with Th2 and Treg polarization. The commencement of steroid therapy dramatically exacerbated clinical manifestations including IgG4-RD-associated HT. The measurement of cytokine and chemokine levels as well as FACS analysis in the development of IgG4-RD seemed to be beneficial. In conclusion, an innovative association of HT, IgG4-RD and vasculitis was observed. This report also offers novel diagnostic and therapeutic approaches for IgG4-RD.
Recently, a subtype of HT has been considered to be a thyroid manifestation of IgG4-RD, although the etiology of IgG4-RD is not established yet.
Immunologically a close association between HT and vasculitis was reported.
Leukocytoclastic vasculitis is a rare skin presentation of IgG4-RD.
In the current case, during the course of HT, IgG4-RD and leukocytoclastic vasculitis occurred; thus, innate immunity and acquired immunity seem to be involved in the development of IgG4-RD.
The measurement of cytokine and chemokines appeared to be beneficial in the development of IgG4-RD.
Remarkably, effectiveness of steroid therapy for HT suggested presence of IgG4-RD-associated HT. Therefore, this report highlights the pathogenesis of IgG4-RD and proposes novel therapeutic mechanisms. Clinicians should pay attention to the development of IgG4-RD and vasculitis during long course of HT.
Immunoglobulin (Ig)G4-related sclerosing disease (IgG4-RSD) is a new disease entity first proposed with regard to autoimmune pancreatitis. A 67-year-old male patient was examined because of weight loss and an abdominal pain. Based on the clinical characteristics, laboratory parameters and ultrasound features, we identified the diagnosis of the IgG4-related systemic disease (IgG4-RSD), that was confirmed by the histopathological analysis after the biopsy of the head of pancreas. After confirmation, we started with the corticosteroid therapy with a good clinical, biochemical and morphological response. During the previous therapy, the disturbance of glucoregulation appeared, so we had to change the modality of treatment. We decided to add Azathioprine to the therapy in a dose of 150 mg/day. We achieved a stable phase of the disease with IgG 4.37 g/l and IgG4 0.179 g/l, and with no side effects from the therapy.
There are potential clinical applications of identifying subsets of patients with IgG4 thyroiditis (FVHT and Riedel thyroiditis).
A trial of immunosuppressive therapy should be included if a resection is deemed inadvisable.
In particular, cases of FVHT that mimic malignancy, tissue and serum IgG4 may provide supportive diagnostic information.
IgG4-related hypophysitis is a recently described entity belonging to the group of IgG4-related diseases. Many other organs can also be affected, and it is more common in older men. To date, 32 cases of IgG4-related hypophysitis have been reported in the literature, 11 of which included confirmatory tissue biopsy and the majority affecting multiple organs. The aim of this report is to present two cases of biopsy-proven IgG4-related hypophysitis occurring in two young female patients with no evidence of involvement of other organs at the time of diagnosis.
IgG4-related hypophysitis belongs to the group of IgG4-related diseases, and is a fibro-inflammatory condition characterized by dense lymphoplasmacytic infiltrates rich in IgG4-positive plasma cells and storiform fibrosis.
It is more common in older men, but young women may also present this type of hypophysitis.
Although involvement of other organs is frequent, isolated pituitary disease is possible.
Frequent clinical manifestations include anterior hypopituitarism and/or diabetes insipidus.
The diagnosis may be confirmed with any of the following criteria: a pituitary biopsy with lymphoplasmacytic infiltrates, with more than ten IgG4-positive cells; a sellar mass and/or thickened pituitary stalk and a biopsy-proven involvement of another organ; a sellar mass and/or thickened pituitary stalk and IgG4 serum levels >140 mg/dl and sellar mass reduction and symptom improvement after corticosteroid treatment.
Glucocorticoids are recommended as first-line therapy.
A 55-year-old male, with a positive medical history for hypothyroidism, treated with stable doses for years was admitted with subacute thyroiditis and a feeling of pain and pressure in the neck. Laboratory tests showed decrease in TSH levels, elevated erythrocyte sedimentation rate, and very high antithyroid antibodies. Owing to enlarging goiter and exacerbation in the patient's complaints, he was operated with excision of a fibrotic and enlarged thyroid lobe. Elevated IgG4 plasma levels and high IgG4/IgG plasma cell ratio on immunohistochemistry led to the diagnosis of IgG4-mediated thyroiditis. We concluded that IgG4-thyroiditis and IgG4-related disease should be considered in all patients with an aggressive form of Hashimoto's thyroiditis.
IgG4-related disease is a systemic disease that includes several syndromes; IgG4-related thyroiditis is one among them.
IgG4-thyroiditis should be considered in all patients with an aggressive form of Hashimoto's thyroiditis.
Patients with suspected IgG4-thyroiditis should have blood tested for IgG4/IgG ratio and appropriate immunohistochemical staining if possible.