ORLANDO—Two novel cases of iatrogenic disease were reported at the American Association of Clinical Endocrinologists 2008 meeting. Michael Gardner, MD, and colleagues described a case of iatrogenic Cushing's syndrome (CS) in a patient who had received two injections of triamcinolone into the sacroiliac joints.¹ Arun Kumar Movva, MD, and Arnold M. Moses, MD, reported a case of substantial hypercalcemia in an osteoporosis patient who was on treatment with teriparatide while also taking hydrochlorothiazide (HCTZ) for hypertension.²

CS following 2 injections of triamcinolone for low back pain

Dr. Gardner described a 40-year-old female patient who had been referred for a rapidly increasing Cushingoid appearance. “She had initially presented for follow-up of low back pain about 6 weeks prior to referral and was noted to have thrush, which was treated with nystatin. A month later, she had gained 32 pounds with a rounding of her face. Also, serum ACTH, 24-hour urine free cortisol, and 8 am serum cortisol, were all below the limits of detection. Upon presentation to our clinic, she was noted to have a round plethoric face, prominent supraclavicular/dorsocervical fat pads, mild proximal muscle weakness, centripetal obesity, and purplish abdominal stria.”

Laboratory tests showed ACTH <2 pg/mL (6-58 pg/mL), 8 am cortisol 0.7 μg/dL (6.7-22.6 μg/dL). On cosyntropin stimulation test (0.25 mg IM), baseline (10 am) cortisol was 1 μg/dL, ½ hour later 5.4 μg/dL, and 1 hour later 6.9 μg/dL.

“Further discussion with the patient revealed injections of 40 mg triamcinolone acetonide on two occasions, 7 and 4 weeks prior to referral, into the sacroiliac joints under fluoroscopic guidance,” Dr. Gardner said.

Urine spectroscopy for synthetic glucocorticoids 2 months following the last injection showed only triamcinolone acetonide at 0.17 μg/dL with no other synthetic glucocorticoids. At 4 months after the last injection, baseline and stimulated cortisol levels had returned to normal, and ACTH levels were normal.

“Previous reports have focused on frequent and/or larger doses of intra-articular or intralesional glucocorticoids. Due to slower absorption modest doses of intra-articular doses of triamcinolone acetonide have been regarded as less likely to cause CS than systemic administration of other glucocorticoids. Following an administration of a routine dose at a routine interval of triamcinolone, our patient developed profound adrenal axis suppression and clinical CS,” Dr. Gardner said. “Intra-articular injections of even modest amounts of high potency steroids can cause iatrogenic CS. We recommend careful monitoring of the adrenal axis in patients receiving these injections.”

Hypercalcemia linked to thiazide diuretic treatment and teriparatide

Dr. Movva's case was a 75-year-old female with history of severe osteoporosis who could not tolerate oral bisphosphonates or IV pamidronate. Pretreatment serum calcium and vitamin D levels were within normal range, as were bone turnover markers, but her bone status steadily worsened on DEXA scans. The patient was taking HCTZ for hypertension. Substantial asymptomatic hypercalcemia developed following institution of teriparatide (Forteo^®) treatment.

“The hypercalcemia resolved once the HCTZ was substituted with a nonthiazide antihypertensive medication,” Dr. Movva said. Baseline serum calcium was 9.3 mg/dL on HCTZ, rose to 12.5 mg/dL 4 to 6 hours after teriparatide, and dropped to 10 mg/dL once a nonthiazide diuretic was substituted for HCTZ and teriparatide was discontinued.
 
“Teriparatide causes hypercalcemia to a modest degree by elevation of the bone turnover markers. The effect is usually transient. Thiazide diuretics are known to increase renal calcium reabsorption. They cause hypercalcemia infrequently because of the compensatory mechanisms. Our case illustrates that patients can be at risk of developing substantial hypercalcemia when they are on both medications. To the best of our knowledge, such an association has never been reported before. Further studies delineating the association are needed…. We recommend careful monitoring of serum calcium levels in patients on thiazide diuretics who are being treated with teriparatide,” Dr. Movva said.

References

1. Gardner M, Kelly R, Lugar R, et al. Iatrogenic Cushing's syndrome from intra-articular injection of triamcinolone acetomide. Presented at: AACE 2008 annual meeting; May 14-17, 2008; Orlando, Fla. Presentation 112.
2. Movva AK, Moses AM. Hypercalcemia resulting from combined use of teriparatide and hydrochlorothiazide. Presented at: AACE 2008 annual meeting; May 14-17, 2008; Orlando, Fla. Presentation 503.