deamino-arginine-vasopressin and Granulomatosis-with-Polyangiitis

Granulomatosis with polyangiitis (GPA) is a necrotizing granulomatous vasculitis of small vessels that affect the pituitary gland in less than 1% of cases being exceptionally rare. To describe the clinical, biochemical, radiological findings, treatment, and outcomes of 4 patients with GPA-related hypophysitis. A systematic review of published cases with the same diagnosis is presented as well. A cross-sectional case series of patients with hypophysitis due to GPA from 1981 to 2018 at a third level specialty center. Literature review was performed searching in seven different digital databases for terms "granulomatosis with polyangiitis" and "pituitary gland" or "hypophysitis," including in the analysis all published cases between 1950 and 2019 with a minimum follow-up of 6 months. We found 197 patients with GPA in our institution of whom 4 patients (2.0%) had pituitary involvement. Clinical characteristics and outcomes are described. We also reviewed 7 case series, and 36 case reports describing pituitary dysfunction related to GPA from 1953 to 2019, including the clinical picture of an additional 74 patients. Pituitary dysfunction due to GPA is rare. Treatment is targeted to control systemic manifestations; nevertheless, the outcome of the pituitary function is poor. Central diabetes insipidus, particularly in younger women with other systemic features, should raise suspicion of GPA.Key Points• Involvement of the pituitary gland is an uncommon manifestation in GPA patients. The presence of central diabetes insipidus in the setting of systemic symptoms should prompt its suspicion.• In patients with pituitary involvement due to GPA, affection of other endocrine glands is rare, neither concomitant nor in different times during the disease course. This may arise the hypothesis of a local or regional pathogenesis affection of the gland.• There is no consensus on the best therapy strategy for GPA hypophysitis. Although the use of glucocorticoids with CYC is the most common drug combination, no differences in the outcome of the pituitary function and GPA disease course are seen with other immunosuppressants.• Poor prognosis regarding pituitary function is expected due to possible permanent pituitary tissue damage that results in the need of permanent hormonal replacement.

Topics: Antidiuretic Agents; Autoimmune Hypophysitis; Deamino Arginine Vasopressin; Diabetes Insipidus, Neurogenic; Female; Glucocorticoids; Granulomatosis with Polyangiitis; Humans; Hyperprolactinemia; Hypopituitarism; Immunosuppressive Agents; Magnetic Resonance Imaging; Male; Middle Aged

GPA with pituitary involvement is a rare condition which is prone to be misdiagnosed. The aim of this study was to summarize clinical features of pituitary involvement in GPA and facilitate early diagnosis. Twelve GPA patients were retrospectively analyzed at a single hospital between 2000 and 2017. A literature review was conducted to compare previous findings with our clinical results. The incidence rate of pituitary involvement in GPA was 3.9% (12/304) without sexual predilection. Other impairments included ear, nose and throat (n = 12), oculi (n = 10), lung (n = 6), meninges (n = 4), kidney (n = 3), and skin (n = 2). Antineutrophil cytoplasmic antibodies (ANCA) were positive in all patients with lung or kidney involvement (n = 6/6), while ANCA were negative in almost all patients without lung or kidney involvement (n = 5/6). Endocrine abnormalities included central diabetes insipidus (CDI, n = 11/12) hypogonadotropic hypogonadism (n = 6/11), adrenocorticotropic hormone deficiency (n = 4/7), thyroid-stimulating hormone deficiency (n = 5/11), and growth hormone deficiency (n = 3/9). Enlarged pituitary gland (n = 6), absence of posterior hyperintense signal on T1-weighed images (n = 11) and hypertrophic cranial pachymeningitis (n = 4) were common radiological manifestations. After treatment, nine patients experienced remission but one died. Pituitary images of 3/4 patients showed size of pituitary lesions decreased. CDI was not alleviated and hypopituitarism remained in two patients. Pituitary involvement in GPA can occur at any time throughout the course of disease, including at the initial presentation. GPA could not be excluded based on negative-ANCA in patients with pituitary abnormality alone. CDI and hypogonadotropic hypogonadism are dominant endocrine abnormalities. Systemic diseases may alleviate and pituitary images may improve after treatment, though the recovery of pituitary function is rare.

Topics: Adult; Antibodies, Antineutrophil Cytoplasmic; Biomarkers; Biopsy; Deamino Arginine Vasopressin; Female; Granulomatosis with Polyangiitis; Hormone Replacement Therapy; Hormones; Humans; Immunosuppressive Agents; Magnetic Resonance Imaging; Male; Middle Aged; Pituitary Diseases; Remission Induction; Retrospective Studies; Thyroxine; Tomography, X-Ray Computed; Treatment Outcome; Young Adult

Desmopressin is a synthetic vasopressin analog that increases the plasma levels of coagulation factor VIII, von Willebrand factor, and tissue plasminogen activator. This hemostatic agent, which can be administered either parenterally or intranasally, has been approved for use in the prevention and treatment of hemorrhagic events during surgery in patients with hemophilia A, in cases of prolonged idiopathic bleeding, and for complications associated with platelet antiaggregant therapy. This case report describes cardiac toxicity associated with desmopressin administered according to the recommended indications: a 55-year-old woman diagnosed with Wegener's granulomatosis (WG) was treated with desmopressin to improve hemostasis and shorten bleeding time before a planned renal biopsy. She developed cardiac arrest within 60 minutes of the desmopressin injection. Cardiopulmonary resuscitation began immediately and was successful, although the patient subsequently died of WG-associated complications. Desmopressin administration thus appears, in some cases, to be associated with a high risk of thrombotic events, possibly by stimulating the rapid release of endothelial factors such as an abnormal multimeric form of von Willebrand factor, which might cause platelet aggregation. Clinicians should be aware of the possible occurrence of this little-known but potentially serious cardiac event associated with desmopressin administration and be prepared to initiate cardiopulmonary resuscitation immediately if needed.

Topics: Biopolymers; Biopsy; Bleeding Time; Deamino Arginine Vasopressin; Disease Progression; Endothelium, Vascular; Fatal Outcome; Female; Granulomatosis with Polyangiitis; Heart Arrest; Hemorrhage; Hemostatics; Humans; Immunosuppressive Agents; Kidney; Middle Aged; Myocardial Infarction; Thromboembolism; Thrombolytic Therapy; von Willebrand Factor

Wegener's granulomatosis (WG) is an anti-neutrophil cytoplasmic antibody (ANCA)-associated systemic vasculitis of small and medium-sized vessels. Pituitary involvement in WG is rare with only 22 previous case reports in the English medical literature between 1966 and 2006. Herein we report another patient with WG-related diabetes insipidus (DI) and partial disruption of the anterior pituitary axes. We also review the clinical features, imaging findings, treatment and outcome of WG-related pituitary involvement. Isolated pituitary involvement in the absence of lung or renal complications in WG is rare and described in only one previous patient. Pituitary involvement in WG is usually associated with other organ involvement (96% of cases)-commonly upper respiratory tract (93%), lungs (73%) and kidneys (67%). Abnormalities are often seen in the hypothalamo-pituitary region on magnetic resonance imaging (MRI) or computed tomography (CT) of the head (90% of cases). In 65% of reported cases, cyclophosphamide-based induction therapy was used with a subsequent relapse rate of 27%, occurring at a median of 10.5 months (range: 7-36 months) after initiation of treatment. In comparison, induction treatment without cyclophosphamide was associated with relapse in 50% at a median of 4.5 months (range: 4-18 months after starting treatment) suggesting more frequent and earlier relapse. Therefore, we recommend treatment with cyclophosphamide-based regimen. Despite treatment of WG, only 17% (4 patients) had full recovery in their pituitary function. The long-term prognosis of patients with WG and pituitary involvement is not known.

Topics: Adult; Antidiuretic Agents; Cyclophosphamide; Deamino Arginine Vasopressin; Diabetes Insipidus, Neurogenic; Drug Therapy, Combination; Glucocorticoids; Granulomatosis with Polyangiitis; Humans; Hypopituitarism; Immunosuppressive Agents; Magnetic Resonance Imaging; Male; Methylprednisolone; Pituitary Function Tests; Pituitary Gland; Recurrence; Treatment Outcome

Topics: Adult; Cyclophosphamide; Deamino Arginine Vasopressin; Diabetes Insipidus; Drug Therapy, Combination; Female; Granulomatosis with Polyangiitis; Humans; Prednisolone