Endocrine Abstracts

Non-classical congenital adrenal hyperplasia (NCCAH) tends to present in adulthood, is more common than classical CAH and is usually associated with a milder presentation. Patients are not usually steroid dependent as the partial enzymatic defects are overcome by elevation in ACTH. Clinical features of hyperandrogenism and metabolic complications overlap with polycystic ovary syndrome (PCOS). Treatment requirements can vary across the lifespan as detailed in the case presented here. At 36 years old, a female patient received a diagnosis of NCCAH following several years of investigations for hirsutism, irregular periods and significant weight gain in her early 30 s. Initial investigations showed a raised testosterone at 3.4 nmol/l (0.5-2.6) and raised 17 OHP (earliest available level 4 years after diagnosis of 13 nmol/l (0-6). Her BMI was 43.2. Genetic testing later in life confirmed pathogenic variants in the CYP21 A2 gene, which results in 21-hydroxylase deficiency. Her short synacthen test (SST) was normal, with a basal cortisol of 315 nmol/l rising to a peak of 500 nmol/l. Dexamethasone was commenced at a low dose of 0.25 mg per night which successfully treated her hirsutism (this was prior to the CaHASE study published in 2010). After nine years of treatment, the patient developed hypertension and complained of difficulty losing weight; BMI was 46.9. Testosterone was undetectable at <0.5 nmol/l and 17 OHP was low-normal at 1.5 nmol/l. She gradually reduced the frequency of dexamethasone and stopped this in her late 40 s. There was a break in treatment until the age of 54, when she complained of excessive fatigue and ongoing difficulty losing weight; BMI was 52.8 and Epworth score was 14. 17 OHP was raised at 23.8 nmol/l, Androstenedione was raised at 3.5 nmol/l (0-3.0) and testosterone was normal at 1.2 nmol/l. At 56 years old her SST showed a suboptimal cortisol response, rising from 237 to 334 nmol/l, and she commenced hydrocortisone. At the age of 58 she commenced HRT to manage symptoms of night sweats, fatigue and reduced libido. Testosterone, 17 OHP and androstenedione were within the normal range, suggesting over-replacement with hydrocortisone. She has been diagnosed with Type 2 diabetes (HbA1 c 50 mmol/mol) and recently commenced Tirzepatide to facilitate weight loss. Ongoing reduction in hydrocortisone dose is currently being attempted. Optimal management of cases with NCCAH remains to be elucidated and an individualised approach is recommended. Temporary treatment with steroids can be effective at managing hyperandrogenism or cortisol deficiency, but must be balanced against the pre-existing increased risk of metabolic complications.