Copeptin Rules Out Diabetes Insipidus Post Pituitary Surgery

Copeptin Rules Out Diabetes Insipidus Post Pituitary Surgery

The study covered in this summary was published on Research Square as a preprint and has not yet been peer reviewed.

Key Takeaways

  • A study of 78 patients who underwent elective transsphenoidal adenomectomy to remove a pituitary tumor or other lesions within the pituitary fossa at a single center in the UK suggests that postoperative plasma levels of copeptin — a surrogate marker for levels of arginine vasopressin (antidiuretic hormone) — can rule out development of central (neurogenic) diabetes insipidus caused by a deficiency of arginine vasopressin following pituitary surgery.

  • The researchers suggest using as a cutoff a copeptin level of >3.4 pmol/L at postoperative day 1 to rule out diabetes insipidus. Such a cutoff yields the following:

    • A high sensitivity of 91% for ruling out diabetes insipidus.

    • A negative predictive value of 97%. Only 1 of 38 patients with a copeptin value >3.4 pmol/L at day 1 postoperatively developed diabetes insipidus.

    • A low specificity of 55%, meaning that copeptin level is not useful for diagnosing diabetes insipidus

    Why This Matters

    • An estimated 1% to 67% of patients who undergo pituitary gland surgery develop diabetes insipidus, often soon after surgery, although it is often transient.

    • Diagnosing diabetes insipidus in such patients requires a combination of clinical assessment, the monitoring of fluid balance, and determining plasma and urine sodium and osmolality.

    • Currently, clinical laboratories in the UK do not have assays for arginine vasopressin, which has a short half-life in vivo and is unstable ex vivo, even when frozen, and is affected by delayed or incomplete separation from platelets.

    • Copeptin, an arginine vasopressin precursor, is much more stable and measurable by commercial immunoassays.

    • The findings suggest that patients who have just undergone pituitary gland surgery and are otherwise healthy and meet the copeptin cutoff for ruling out diabetes insipidus could be discharged 24 hours after surgery and that there is no need for additional clinical and biochemical monitoring. This change would ease demands on the healthcare system.

    Study Design

    • The study reviewed 78 patients who underwent elective transsphenoidal adenomectomy to remove a pituitary tumor from November 2017 to June 2020 at the John Radcliffe Hospital in Oxford, United Kingdom.

    • Patients remained in hospital for a minimum of 48 hours after their surgery.

    • Clinicians collected blood and urine specimens preoperatively and at day 1, day 2, day 8, and week 6 post surgery.

    • The patients were restricted to 2 L of fluid a day postoperatively to prevent masking of biochemical abnormalities through compensatory drinking.

    • Diabetes insipidus was suspected when patients’ urine output was >200 mL/h for 3 consecutive hours or >3 L/d plus high plasma sodium (>145 mmol/L) and plasma osmolality (> 295 mosmol/kg) plus inappropriately low urine osmolality. Definitive diagnosis of diabetes insipidus was based on clinical assessment, urine and plasma biochemistry, and need for treatment with desmopressin (1-deamino-8-D-arginine vasopressin).

    Key Results

    • The median age of the patients was 55, and 53% were men; 92% of the lesions were macroadenomas; the most common histologic type was gonadotroph tumor (47%).

    • Among the 78 patients, 11 (14%) were diagnosed with diabetes insipidus postoperatively and required treatment with desmopressin; of these, seven patients (9%) continued taking desmopressin after 6 weeks (permanent diabetes insipidus), but the other four did not need to take desmopressin for more than a week.

    • Patients who developed diabetes insipidus were younger than other patients (mean age, 46 vs 56), and 8 of the 11 patients who developed diabetes insipidus (73%) were women.

    • Preoperative copeptin levels were similar in the two groups. At day 1, day 8, and 6 weeks postoperatively, copeptin levels were significantly lower in the diabetes insipidus group; there were no significant differences at day 2, largely because of an outlier result.

    • An area under the receiver operating characteristic curve (AUC; C-statistic) analysis showed that on day 1 after surgery, copeptin levels could account for 74.22% of the incident cases of diabetes insipidus (AUC, 0.7422). On postop day 8, the AUC for copeptin was 0.8015, and after 6 weeks, the AUC associated with copeptin was 0.7321.

    Limitations

    • Blood samples for copeptin tests from patients who underwent pituitary surgery were collected at specified times and were frozen for later analysis; performing the test in real time might alter patient management.

    • The study may have missed peak copeptin levels by not determining copeptin levels sooner after pituitary gland surgery, inasmuch as other researchers have reported better predictive values for diagnosing diabetes insipidus from samples taken 1 hour after extubation or <12 hours after surgery.

    Disclosures

    • The study did not receive commercial funding.

    • The authors report no relevant financial relationships.

    This is a summary of a preprint research study, “Post-Operative Copeptin Analysis Predicts Which Patients Do Not Develop Diabetes Insipidus After Pituitary Surgery,” by researchers from John Radcliffe Hospital, Oxford University Hospitals NHS Foundation Trust, in the United Kingdom. Preprints from Research Square are provided to you by Medscape. This study has not yet been peer reviewed. The full text of the study can be found on researchsquare.com.

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