Infection with SARS-CoV-2 may alter the half-life of desmopressin (DDAVP) in patients with central diabetes insipidus

Introduction

Central diabetes insipidus (CDI) is characterised by a central deficiency of arginine vasopressin (AVP). Typical symptoms of manifestation are polyuria and polydipsia [1]. Polyuria is defined as urine output of more than 2 L per square meters of body surface area per 24 h [2]. The etiology of CDI is very heterogeneous and comprises germinoma, craniopharyngeoma, sarcoidosis, Langerhans cell histiocytosis, surgery, trauma, inflammatory diseases, autoimmune diseases, vascular diseases, metastases, midline cerebral and cranial malformations or rare genetic conditions [1], [2], [3], [4], [5], [6], [7]. However, in 20–50% of cases, no cause can be identified [1, 2, 8]. Typical, but not specific, radiological findings can be the absence of hyperintensity of the posterior pituitary gland on sagittal T1-weighted magnetic resonance imaging (MRI). In addition, a thickened infundibulum or pituitary stalk can be found [1]. The treatment of choice in childhood is the oral or nasal application of DDAVP (synthetic analogue of AVP) [1]. The nasal dosage of DDAVP in children is typically 2–40 µg once or twice a day [2]. Some authors have already pointed out the particularities and difficulties of caring for patients with CDI during the SARS-CoV-2 pandemic [9]. CDI as a consequence of COVID19 has also already been reported in an individual case [10]. To the best of our knowledge, there have been no reports of a change in DDAVP half-life or effect in the context of coronavirus disease 2019 (COVID19).

Case presentation

We present a 9-year old male with CDI of uncertain aetiology. The boy first presented to our emergency department in November 2020. The medical history was without any previous illnesses, trauma or drug therapy. The reason for presentation was polydipsia (maximum of 5 L of oral fluid intake per day) and polyuria. Diabetes mellitus could be excluded due to normal blood glucose levels, normal values for HbA1c and absence of glucosuria. The polydipsia and polyuria also manifested at night. A detailed clinical work-up was performed. MRI of the head showed a nodular thickening of the pituitary stalk and lack of T1w hyperintensity of the neurohypophysis (Figure 1). No evidence of sarcoidosis or Langerhans cell histiocytosis was found. In addition, we performed a positron emission tomography/computed tomography (PET/CT). No evidence of a malignoma-typical metabolically active tumour or any other metabolically active systemic diseases could be found. As expected, the level of CT-proAVP (copeptin) in serum was very low, namely below 2.7 pmol/L (despite increased osmolality in the serum of 306 mosm/kg). The value for sodium in the serum was high with a maximum of 151 mmol/L, which was well compatible with the underlying disease. The values for IGF1 and IGFBP3 were also low in the sense of an affection of the corresponding hormone axis. Further laboratory analysis showed no involvement of the thyroid or gonadotropic axis. To rule out hypocortisolism, we performed a corticotropin-releasing hormone test (CRH test). This showed a normal result with a cortisol increase of >7.2 μg/dL and an adrenocorticotropic hormone (ACTH) increase of at least 50%. In addition, another abnormal laboratory value was prolactin with a maximum of 813 µU/mL (normal range <324 µU/mL). It is possible that the increase of prolactin levels is related to the thickening of the pituitary stalk, which in turn may cause reduced dopaminergic inhibition of prolactin secretion. Further laboratory tests including blood count, clinical chemistry, coagulation and urine metanephrines were without pathological findings.

Figure 1:

Pituitary gland on sagittal T1-weighted magnetic resonance imaging (MRI) with thickened pituitary stalk in a 9 year old boy with central diabetes insipidus (CDI).

Drug therapy was initiated with DDAVP at 1.2 µg in the morning and 0.6 µg in the evening. The application form was nasal. This treatment showed normalisation of polyuria and polydipsia and normalisation of serum sodium levels. After initiating treatment, the daily drinking quantity was about 2 L per day. Also, no more nocturia was observed.

In the course of the therapy, a multiple dose increase became necessary. The most recent dose was 6 µg in the morning and 1.8 µg in the evening. Multiple follow-up controls by MRI showed a regressive thickening of the pituitary stalk.

In November 2021, the patient complained of severe sore throat one evening. The pain was completely gone the following morning. Two days after the onset of symptoms, a rapid antigen test was positive for SARS-CoV-2. This test was performed routinely at school. A PCR examination in our clinic also confirmed the infection with SARS-CoV-2. The variant analysis by means of mutation PCR resulted in a high-grade suspect of SARS-CoV-2 VoC line B.1.617.2 (Delta) with mutations in the spike genes L452R and P681R (38,000 copies/mL in saliva analysis).

Surprisingly, with the onset of the sore throat, the half-life of the usual dosage of DDAVP therapy was significantly prolonged. Thus, the boy received the usual 1.8 µg of desmopressin nasally in the evening (day of onset of symptoms). The effect, which usually ceased the following morning, lasted until next day 1 p.m. at noon. Thus, the duration of action was prolonged by approximately 6 h. The morning dose was skipped. The evening dose of 1.8 µg was then administered again at 1 p.m. at noon. This lasted until the following morning 7 a.m. Thus, the duration of action was prolonged again by approximately 6 h. A check of serum sodium during this time showed a normal result at the upper limit of normal (147 mmol/L). After three days, the regular dosage could be reintroduced (6 µg in the morning and 1.8 µg in the evening). The usual times of action were again evident.

Discussion

Our case report shows the case of a boy with a good therapy adjustment with DDAVP of CDI. In the context of a clinically very mild infection with SARS-CoV-2, the half-life of DDAVP was significantly prolonged with the onset of mild clinical symptoms. It is possible that there is a causal connection to the infection. A plausible explanation for the altered half-life would be an altered nasal mucosa in the context of an involvement of the upper respiratory tract and thus an altered resorption of DDAVP. However, the patient did not report any symptoms in the nasal region and the clinical examination did not reveal any abnormal findings in the ENT region. Furthermore, there was no adjustment of the dosage and no change of the manufacturer, the pharmacy, the application or storage of the preparation in the temporal context.

Our case report is of great clinical relevance, as even mild COVID19 diseases may lead to a change in DDAVP duration of action. Clinicians should ask patients with CDI in the context of the COVID19 pandemic about changes in drinking behaviour, diuresis and duration of drug action. This may reduce the risk of symptomatic dilutional hyponatremia, a feared adverse effect of therapy.