Adrenal Vein Sampling in a Patient With Primary Hyperaldosteronism and Severe Contrast Allergy

Margaretha L.M. Prins; Bartholomeus E.P.B. Ballieux; Onno C. Meijer; Alberto M. Pereira; Michiel F. Nijhoff


J Endo Soc. 2021;5(10) 

In This Article


Here we demonstrate that successful and reliable AVS is possible in patients with severe PA and a known allergy to ICM if high-dose dexamethasone with concomitant continuous ACTH infusion is used.

Distinguishing the subtype of PA is key to determine the best treatment options. AVS is generally required to differentiate between unilateral and bilateral disease.[17,21] ICM is essential for successful angiographic localization of the adrenal veins. ICM is generally safe, but adverse hypersensitivity reactions (HSR) after the administration of ICM are a continuous challenge in clinical practice. Adverse events after ICM exposure are classified into immediate HSR (onset immediately up to 1 h after administration of the agent and presents with symptoms of anaphylaxis) and nonimmediate HSR (start more than 1 h up to 10 days after administration and presents with exanthems), with different mechanisms. Reported data of previous studies have shown that the incidence of acute adverse reactions to ICM varied widely because of different definitions. Reported incidence rates are 0.15% to 2% with low-osmolarity contrast agents, with >98% being mild and self-limiting.[22–29] Battistel et al found that 2.6% of patients with PA selected for AVS reported a history of severe ICM allergy requiring premedication.[30] Several risk factors for developing repeat reaction to ICM are being discussed. The commonly agreed-on risk factor is a history of an immediate adverse reaction to the ICM.[28,29,31,32] Park et al found that patients with severe initial HSR exhibit a higher recurrence rate of severe HSR compared to patients with moderate initial HSR.[29]

Alternative methods that permit invasive imaging of adrenal veins are required in patients with contraindication to ICM. One potential method is the use of gadolinium as an alternative contrast agent. The use of gadolinium contrast to visualize visceral, peripheral, carotid, or coronary arteries has been reported in patients with contraindications for ICM or renal insufficiency.[33–35] Sasamura et al reported the use of gadolinium for venography of the adrenal veins in a patient with ICM allergy without any side effects.[36] A reaction to both ICM and gadolinium is believed to be a rare event[37] because they are chemically distinct compounds with structural differences. In 1 study, the incidence rate of acute allergic-like reactions to both agents in patients who have received both types of contrast media for imaging studies was reported.[37] The overall incidence rates of reaction to ICM and gadolinium were 0.48% and 0.17%, respectively; 0.024% of patients had reactions to both ICM and gadolinium. None of the reactions was reported to be moderate or severe.

Mistuba et al described 2 cases of PA patients in which gadopentetate dimeglumine, gadolinium chelated by diethylenetriamine pentaacetate, was used as an alternative contrast agent for AVS.[38] The results showed reduced, but acceptable quality. No adverse reaction occurred.

Battistel et al demonstrated the feasibility of another strategy to circumvent the need for ICM.[30] They used carbon dioxide (CO2) administration to visualize the inferior vena cava and the adrenal veins and to verify the correct placement of the catheter's tip within the vessels. Similar to gadolinium, CO2 has been used as a radiocontrast agent, and it can be used in patients with renal dysfunction or ICM allergy. The AVS procedure was successful. However, CO2 gas is technically difficult to use, and the image resolution may be inferior.[39]

The visualization of the adrenal veins in these reports was considerably poorer than the images obtained using conventional contrast media. We did not choose these methods because of the reduced image quality and a lack of experience with the use of these contrast media for AVS at our center.

We are the first to report on a simplified strategy to safely perform AVS with continuous ACTH infusion in patients with ICM allergy using dexamethasone as premedication, instead of prednisolone or hydrocortisone.

The Elecsys Cortisol II assay in our clinical laboratory is an automated competitive immunoassay using a monoclonal antibody, which is highly specific for cortisol. Of all automated immunoassays, the Elecsys Cortisol II is probably the least affected by interference with synthetic glucocorticoids. However, therapy with prednisolone, 6-α-methylprednisolone or prednisone can still result in falsely elevated concentrations of cortisol, due to their close similarity to cortisol.[19] Dexamethasone and other fluorinated corticosteroids exert no significant cross-reactivity in this assay and in all other cortisol immunoassays used in clinical practice. Therefore, it is the glucocorticoid of choice in suppression tests of the hypothalamic-pituitary-adrenal axis to assess hypercortisolism.

Dexamethasone binds to glucocorticoid receptors in hypothalamic paraventricular nuclei and in pituitary corticotroph cells, and as such, glucocorticoids exert negative feedback effects on the hypothalamic-pituitary-adrenal axis via direct suppression of corticotropin-releasing hormone and ACTH secretion. Under physiological circumstances, a supraphysiologic dose of any glucocorticoid, including dexamethasone, is sufficient to suppress pituitary ACTH secretion and thus cortisol production. It is, however, not clear if there is a direct inhibitory effect of dexamethasone on the adrenal cortex, although dexamethasone has been shown to inhibit the transcription of steroidogenic genes through a mechanism that involved glucocorticoid receptor– and steroidogenic factor 1–mediated induction of DAX-1.[40] To our knowledge, there are no published reports on the concomitant use of dexamethasone and ACTH, 2 agents with opposite mechanism of action on adrenal cortisol production. Therefore, a high-dose ACTH stimulation test during short-term treatment with dexamethasone was performed according to clinical practice guidelines of the Endocrine Society.[41] A peak of serum cortisol >430 nmol/L is considered normal using the restandardized Roche Elecsys Cortisol II assay, which is calibrated against the international reference method for cortisol.[19,42] The observed peak stimulated cortisol of 812 nmol/L in our patient indicated excellent adrenal secretory response despite the presence of high-dose dexamethasone.

The main limitation of this report is that our analysis is restricted to 1 patient. Our finding thus requires further confirmation. Another limitation is that it there is a lack of research on how administration of dexamethasone affects the release of aldosterone.