Compliance Issues in Managing 21 Hydroxylase Deficiency and their Short/Long-Term Consequences.

OBJECTIVE: To report a case of untreated classic 21 hydroxylase (OH) deficiency congenital adrenal hyperplasia (CAH) in a transgender patient resulting in pulmonary embolisms (PEs) and bilateral adrenal masses. METHODS: A 36-year-old male (birth sex: female) presenting with bilateral PEs in the setting of long-standing, untreated classic 21OH CAH was also found to have bilateral adrenal masses (unconfirmed myelolipomas). RESULTS: Further history revealed a known diagnosis of CAH. The patient had been treated with glucocorticoid and mineralocorticoid replacement in childhood but stopped taking these medications against medical advice. During his hospital admission, he was noted to have elevated 17-hydroxyprogesterone, low cortisol with elevated ACTH levels, and male-level testosterone measurements. CT of the abdomen/pelvis revealed a 23 cm mass in the left renal fossa and a 2.5 cm mass in the right renal fossa consistent with bilateral adrenal myelolipomas. The patient attended follow-up in clinic, but declined any further hormonal treatment as he identified as male and felt further treatment was unnecessary. CONCLUSION: This case demonstrated the unique long-term effects of untreated classic CAH due to 21OH deficiency, including bilateral adrenal myelolipoma, adrenal compensation to the point of producing male-level androgens, and possibly PEs. Treatment with hydrocortisone was recommended to suppress ACTH and it was planned that the patient would eventually start on testosterone (although this would have been complicated by his bilateral PEs). Potential aetiologies for the PEs included vascular compression of the renal artery (which could explain the elevated EPO/erythrocytosis contributing to hypercoagulability) or the renal vein by the adrenal mass. LEARNING POINTS: Gender dysphoria in patients with congenital adrenal hyperplasia (CAH) is not uncommon.Adrenal enlargement can allow untreated CAH patients to compensate.Pulmonary embolisms can be a consequence of treating as well as untreated CAH.

LDLR promoter variant and exon 14 mutation on the same chromosome are associated with an unusually severe FH phenotype and treatment resistance.

Familial hypercholesterolemia (FH) is the most common form of autosomal-dominant hypercholesterolemia, and is caused by mutations in the low-density lipoprotein receptor (LDLR) gene. Heterozygous FH is characterized by elevated low-density lipoprotein (LDL) cholesterol and early-onset cardiovascular disease, whereas homozygous FH results in more severe LDL cholesterol elevation with death by 20 years of age. We present here the case of an African-American female FH patient presenting with a myocardial infarction at the age of 48, recurrent angina pectoris and numerous coronary artery stents. Her pretreated LDL cholesterol levels were more typical of a homozygous FH pattern and she was resistant to conventional lipid-lowering treatment, yet her other clinical parameters were not necessarily consistent with homozygous FH. Genetic testing revealed two LDLR variants on the same chromosome: one a novel missense mutation in exon 14 (Cys681Gly) and the other a promoter variant (IVS1-217C>T) previously shown to result in increased LDLR transcription. Disease-associated PCSK9 or APOB mutations were not identified in this individual. Overall, her genetic and clinical profile suggests that enhanced expression of the mutant LDLR allele resulted in a severe phenotype with characteristics of both heterozygous and homozygous FH.