A 37-year-old female patient, with previous diagnosis of rheumatoid arthritis, was under well tolerated therapy with adalimumab (40 mg twice a month since December 2018). She had no other relevant medical, surgical or familial history. She was in her usual state of health when she has received the second dose of BNT162b2 mRNA COVID-19 vaccine (June 2021). Seven days later, she started reporting intense thirst and polyuria and consulted her family physician. She denied headache, polyphagia, weight loss, foamy urine, macroscopic hematuria, peripheral or periorbital edema. On physical examination: blood pressure 120/80 mmHg, heart rate 70 bpm, weight 60 kg and height 165 cm; cardiac and pulmonary auscultation were normal and she had no relevant abnormalities. She was then referred to the Nephrology Department of her local hospital.
Blood analysis: creatinine 0.7 mg/dL, glucose 95 mg/dL, Na+ 141mEq/L, K+ 3.9 mEq/L, Calcium 8.9 mg/dL, Albumin 42 g/dL, TSH 3.8 mcUI/L (0.38-5.33), FT4 0.9 ng/dL (0.6-1.1), cortisol (8 am) 215.4 nmol/L (185-624), ACTH 21.9 pg/mL (6-48), osmolality 298.2 mOs/Kg (250-325); Urine analysis: volume 10200 mL/24h, osmolality 75 mOs/Kg (300-900), density 1.002.
Due to these findings, diabetes insipidus was suspected and she was then admitted to the Nephrology ward to perform a water deprivation test. This test is based on an indirect assessment of AVP activity using urine concentration capacity measurements during a lengthy period of dehydration and again after injection of desmopressin. Hourly measurements of body weight and urine osmolality are taken during water restriction until 2-3 samples differ by less than 30 mOsm/kg, or the patient loses more than 3% of his or her body weight, or plasma Na+ surpasses 145 mEq/L. Desmopressin is then injected. The osmolality of the urine is tested 60 minutes later. CDI and nephrogenic DI are distinguished by their responses to desmopressin treatment. Complete nephrogenic DI is diagnosed when urine osmolality remains below 300 mOsm/kg after thirst and does not increase by more than 50% following desmopressin administration. If the urine osmolality rises by more than 50% following desmopressin administration, complete CDI is identified. Urinary concentration rises to 300-800 mOsm/kg in partial CDI and primary polydipsia, with increments of >9% (in partial CDI) and 9% (in primary polydipsia) after desmopressin injection.
The water deprivation test started at 08.00 a.m. of the day after admission. The results showed: serum basal Na+ 141 mEq/L; serum basal osmolality of 308.8 mOsm/Kg; serum basal AVP below detection limit of 0.8 pg/mL; basal urine osmolality: 68.0 mOsm/Kg; At 60 min. Na+ 147 mEq/L and urine osmolality 61 mOsm/Kg; 1 h after 2 mcg of intravenous desmopressin: urine osmolality was 511 mOsm/Kg and Na+ 139 mEq/L. ( Figure 1 ) The Endocrinology Department was contacted for clinical guidance. Further hormonal analysis showed: FSH 4.76 UI/L, LH 5.62 UI/L, estradiol 323 pmol/L, IGF1 74.8 ng/mL (88-209), PRL 24.7 mcg/L (3.3-26.7). MRI of the pituitary gland revealed loss of the posterior pituitary bright spot on T1 weighted imaging. ( Figure 2 ) Diagnosis of CDI was assumed, and she started therapy with oral desmopressin 0.06 mg twice a day. Although pituitary biopsy was not conducted, other probable causes of CDI were ruled out - serum levels of iron, IgG4, angiotensin-converting enzyme and beta2-microglobulin were normal. Infection by mycobacterium tuberculosis was also ruled out. A report of this potential adverse effect from BNT162b2 mRNA COVID-19 vaccine was addressed to national health authorities. On the last appointment (December 2021), she was under oral desmopressin 0.06 mg three times a day, had no polydipsia or polyuria, blood pressure was 110/80 mmHg, and analytical results showed a serum osmolality of 297.2 mOsm/kg, and urine osmolality of 148.0 mOsm/kg. Desmopressin was then titrated to 0.12 mg twice a day. Reevaluation of anterior pituitary function was normal: TSH 2.62 mcUI/L, FT4 0.89 ng/dL, cortisol 8 a.m. 302 nmol/L, IGF1 78 ng/mL, FSH 5.7 UI/L, LH 5.8 UI/L, estradiol 412 pmol/L.