AVP deficiency (central diabetes insipidus) following immunization with anti-COVID-19 BNT162b2 Comirnaty vaccine in adolescents: A case report

Abstract

IntroductionThe coronavirus disease 19 (COVID-19) pandemic has prompted the development of new vaccines to reduce the morbidity and mortality associated with this disease. Recognition and report of potential adverse effects of these novel vaccines (especially the urgent and life-threatening ones) is therefore essential.Case presentationA 16-year-old boy presented to the Paediatric Emergency Department with polyuria, polydipsia and weight loss over the last four months. His past medical history was unremarkable. Onset of symptoms was referred to be few days after first dose of anti-COVID-19 BNT162b2 Comirnaty vaccine and then worsened after the second dose. The physical exam was normal, without neurological abnormalities. Auxological parameters were within normal limits. Daily fluid balance monitoring confirmed polyuria and polydipsia. Biochemistry laboratory analysis and urine culture were normal. Serum osmolality was 297 mOsm/Kg H2O (285-305), whereas urine osmolality was 80 mOsm/Kg H2O (100-1100), suggesting diabetes insipidus. Anterior pituitary function was preserved. Since parents refused to give consent to water deprivation test, treatment with Desmopressin was administered and confirmed ex juvantibus diagnosis of AVP deficiency (or central diabetes insipidus). Brain MRI revealed pituitary stalk thickening (4 mm) with contrast enhancement, and loss of posterior pituitary bright spot on T1 weighted imaging. Those signs were consistent with neuroinfundibulohypophysitis. Immunoglobulin levels were normal. Low doses of oral Desmopressin were sufficient to control patient’s symptoms, normalizing serum and urinary osmolality values and daily fluid balance at discharge. Brain MRI after 2 months showed stable thicken pituitary stalk and still undetectable posterior pituitary. Due to persistence of polyuria and polydipsia, therapy with Desmopressin was adjusted by increasing dosage and number of daily administrations. Clinical and neuroradiological follow-up is still ongoing.ConclusionHypophysitis is a rare disorder characterized by lymphocytic, granulomatous, plasmacytic, or xanthomatous infiltration of the pituitary gland and stalk. Common manifestations are headache, hypopituitarism, and diabetes insipidus. To date, only time correlation between SARS-CoV-2 infection and development of hypophysitis and subsequent hypopituitarism has been reported. Further studies will be needed to deepen a possible causal link between anti-COVID-19 vaccine and AVP deficiency.

Hypopituitarism with secondary adrenocortical insufficiency and arginine vasopressin deficiency due to hypophysitis after COVID-19 vaccination: a case report

“…There is no description of the recovery of hormone levels in the three previous cases of hypopituitarism induced by COVID-19 vaccines [ 11 – 13 ]. In some cases of AVP deficiency, long-term replacement of vasopressin is necessary [ 6 – 8 , 11 ]. Nevertheless, it is also reported that in about half cases of thyroid disorder, at least partial recovery was observed within 5 months [ 11 ], indicating a relatively better prognosis in ASIA than other etiologies.…”

“…These vaccines can cause various side effects such as pain, swelling, fever, headache, and diarrhea [2]. Regarding the pituitary gland, pituitary apoplexy [3][4][5] and arginine vasopressin (AVP) deficiency [6][7][8][9][10][11] have rarely been reported after COVID-19 vaccination. Only three cases of hypophysitis and anterior pituitary hormone deficiency have been reported: low insulin-like growth factor [11], isolated adrenocorticotropic hormone (ACTH) deficiency [12], and anterior hypopituitarism [11,13].…”

SARS-CoV-2 Vaccines-Related Endocrine Disorders: An Updated Narrative Review

“…Pituitary disorders were initially reported in the setting of SARS-CoV2 infection, followed by published clinical cases of hypophysitis, central diabetes insipidus, SIADH, pituitary apoplexy, and ACTH deficiency as rare adverse effects of the vaccination. The summarized cases of pituitary conditions are not very numerous, but perhaps the actual incidence is underreported and thus underestimated [85][86][87][88][89][90][91][92][93][94][95][96][97][98][99][100][101][102][103][104]. In addition, a delay in diagnosis can arise from overlapping symptoms related to pituitary hormone deficiencies and those experienced after vaccination.…”

“…Concerning hypophysitis, this is a sporadic disease with an incidence of ~1 in 9 million/year in the form of primary hypophysitis [96]. Hypophysitis following SARS-CoV-2 vaccine present most often as isolated arginine vasopressin (AVP) deficiency (central diabetes insipidus) due to infundibuloneurohypophysitis [89,[97][98][99]. AVP deficiency was also reported with subsequent development of optic neuritis [100].…”

Hypophysitis after COVID-19 vaccination in a patient with Rathke’s cleft cyst: A case report

“…Several types of COVID-19 vaccines, such as mRNA, adenoviral vectors and inactivated vaccines, have been marketed in various countries to reduce infection and mortality rates. It is not clear whether there is an increased risk of endocrine disease morbidity after vaccination, but some endocrine diseases were reported after vaccination, such as type 1 diabetes mellitus, 4 thyroiditis, 5 Graves’ disease, 6 AVP deficiency (central urolithiasis), 7 optic neuritis and pituitary inflammation comorbidities, 8 , 9 and even adrenal crisis secondary to COVID-19 vaccination in patients with hypopituitarism. 10 In this paper, we report a case of hypophysitis after COVID-19 vaccination in a patient with Rathke’s cleft cyst to raise attention to the rare but serious adverse reactions for early recognition and intervention.…”