PMON17 Impaired cortisol regulation in Myotonic dystrophy

Abstract

Abstract Introduction - Myotonic dystrophy (MD) is the most common cause of adult-onset muscular dystrophy. It has impaired HPA axis regulation with exaggerated ACTH response to CRH mediated stimuli and abnormal cortisol metabolism. We present a case of myotonic dystrophy in a male with elevated cortisol levels. Case report - 54-year-old male with a past medical history of type 1 myotonic dystrophy (MD1) presented for evaluation of hypogonadism with complaints of feeling fatigued, progressive weakness of muscles. During the workup, he was noted to have elevated cortisol levels 30.2 mcg/dL (6-18.4) with elevated ACTH 220 pg/mL (10-48). Other notable lab results included low total testosterone levels of 231, 185 with elevated LH of 17.3 m IU/ml (2-9) and FSH 37.7 m IU/ml (1-12). Prolactin levels were minimally elevated to 21.4 ng/mL (4-15.2). On further inquiry, the patient did not have headaches or vision changes. The patient did not report weight gain, easy bruising, change in facial appearance. Physical exam was significant for bilateral gynecomastia and small testes. No cushingoid facies, abdominal stria, proximal myopathy was noted. Given elevated ACTH and cortisol levels, further laboratory data showed a lack of suppression of cortisol levels with 1 mg dexamethasone - cortisol 2.9 micro g/dL (<1.8), elevated midnight salivary cortisol - 0.130, 0.102 ug/dl (0.010-0.090), and normal 24-hour urine cortisol levels -15 mcg/24 hours. Discussion – Even though Cushing's disease is one of the differential diagnoses for the above case, high cortisol levels have been reported in MD. Few mechanisms suggested causing this abnormality are increased ACTH responsiveness to CRH-mediated stimuli and abnormal cortisol metabolism. Patients with MD have high pro-inflammatory (IL-1 and TNF-a) markers, which mediate the increased ACTH responsiveness to CRH-mediated stimuli centrally by stimulating the HPA axis.1 In addition, IL-6 chronically stimulates steroidogenesis from the adrenal gland, whereas TNF-α inhibits ACTH-induced adrenal steroid synthesis and increases 11BHSD1 activity. Along with the impaired HP axis, abnormal metabolism of cortisol also contributes to elevated cortisol levels. Increased activity of 11 BHSD1 has been hypothesized to cause impaired clearance of cortisol.2 Impaired diurnal variation for cortisol is also seen in MD with elevated 24-hour cortisol levels. Elevated cortisol levels as in our case can be a diagnostic dilemma given impaired cortisol regulation as seen in MD. References Åsa Johansson et.al. Abnormal Cytokine and Adrenocortical Hormone Regulation in Myotonic Dystrophy, The Journal of Clinical Endocrinology & Metabolism, Volume 85, Issue 9, 1 September 2000, Pages 3169–76.Åsa Johansson et.al. Glucocorticoid Metabolism and Adrenocortical Reactivity to ACTH in Myotonic Dystrophy, The Journal of Clinical Endocrinology & Metabolism, Volume 86, Issue 9, 1 September 2001, Pages 4276–83 Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.