Endocrine Abstracts

Primary pigmented nodular adrenocortical disease (PPNAD) is a rare form of ACTH-independent Cushing’s syndrome (CS). Approximately 30% of patients with PPNAD are sporadic cases and the other are familial. We describe a case of a patient affected by PPNAD presenting with isolated arterial hypertension. A 19-year-old black female patient was referred to the Endocrinology Unit in september-2021 due to severe arterial hypertension and fatigue. Previous clinical history was unremarkable and physical examination did not reveal typical signs of hypercortisolism. The echocardiogram revealed mild cardiac hypertrophy and antihypertensive treatment was started, but the subsequent laboratory tests revealed: normal potassium levels, increased midnight salivary cortisol levels (MSC 10-8.9-10.1 nmol/l n.v. <2.8), increased cortisol levels after both 1 mg and 8 mg dexamethasone suppression test (15 mg/dl, 20.1 mg/dl respectively), low plasma ACTH levels (1.5 ng/l; n.v.: 8-50) and increased urinary free cortisol excretion (81.5 mg/24h n.v.<43), with aldosterone and renin levels within normal ranges. Computed tomography (december-2021), showed a slight enlargement of the left adrenal gland with a 8 mm nodule however, adrenal scintigraphy documented the presence of a bilateral (131)I-norcholesterol, uptake. ACTH-independent CS was diagnosed and treatment with metyrapone was started (750 mg) in order to achieve disease control before surgery. Unfortunately, after a few weeks, the patient complained hypoadrenal symptoms as abdominal pain, nausea, and fatigue worsening even in the presence of normal morning cortisol levels, and the treatment was discontinued. The patient underwent left-sided laparoscopic adrenalectomy (october-2022). Histopathological examination confirmed typical features of PPNAD (multiple cortical solid black nodules of 0.4–2.5 mm). Perioperative hydrocortisone therapy was performed and replacement treatment with cortisone acetate was started before hospital discharge. At the last visit, three months after surgery, adrenal insufficiency was confirmed (morning basal cortisol 8 mg/dl with cortisol peak after Synacthen test 12 mg/dl), ACTH levels were still suppressed, and so were androgens and MSC (1.3 nmol/l). However, blood pressure control was still scarce and antihypertensive treatment was maintained. An extensive follow-up has been scheduled due to the high risk of recurrence. Genetic testing revealed a rare heterozygous missense PDE8B germline mutation, c.219G>C (p.Glu73Asp), inherited from her father who is normotensive and presents normal cortisol levels after 1 mg dexamethasone suppression test.