Endocrine Abstracts

Introduction: In Endocrinology, subclinical disorders meet certain diagnostic laboratory thresholds, but are by definition asymptomatic. Subthreshold disorders in Endocrinology have not been defined. We describe two cases of cortisol deficiency, primary and secondary, with normal baseline cortisol, which were by presentation clinical, but could be characterized as subthreshold by biochemical cut-off criteria.

Case 1: A 47-year-old woman was referred for assessment of adrenal reserve, one year after a complicated admission following a road accident. Her past medical history was remarkable for Hashimoto’s thyroiditis on thyroxine. During her hospitalization with multiple injuries and subdural hematoma, she developed multiple complications, including bilateral adrenal hemorrhage. On examination the patient complained of fatigue; she was hemodynamically stable, but skin and mucosal hyperpigmentation was noted. Multiple measurements of am serum ACTH revealed values between 428–800 pg/ml (10–60) with preservation of circadian rhythm and of cortisol between 10 and 20 ng/ml (6–22). Other relevant labs were: TSH 3.67 mIU/ml, DHEAS 75 μg/dl (150–475), plasma renin activity 13.88 ng/ml/h (0.48–4.88), aldosterone 13.7 ng/dl (4–30). Response to 250 μg tetracosactrin stimulation was borderline at 60’ (17.8 μg/dl). Pituitary MRI was normal. Adrenal CT showed normal/small adrenal glands, with complete resolution of hemorrhage. Antibodies to 21-hydroxylase were negative. Serum cortisol-binding protein was 3.8 mg/dl (1.7–3.1) while on oral contraceptives. She was started on hydrocortisone 10–0–5 mg with resolution of symptoms. Four years following the initial presentation, the patient had an am cortisol of 11.89 ng/ml, ACTH 24.5 pg/ml, DHEAS 21 μg/dl and normal response to tetracosactrin stimulation (0’ 16.2 μg/dl, 30’ 20.16 μg/dl, 60’ 21.77 μg/dl), indicating full delayed recovery of the axis.

Case 2: A 87-year-old woman was hospitalized because of severe fatigue, nausea and associated hyponatremia at 125 mmol/l. Her past medical history was significant for hypertension treated with carvedilol 6.25 bid. Her am serum ACTH and cortisol on repeated measurements were 13.6 pg/ml (10–60) and 11.8 μg/dl respectively. Response to 250 μg tetracosactrin stimulation was borderline at 60’ (17.9 μg/dl). Prolactin was 1.89 ng/ml, TSH 0.255 mIU/l, FT4 0.61 ng/dl (0.6–1.49) and FSH 1.79 mIU/ml. Pituitary MRI was normal. The cause of hypopituitarism remained unknown. She was started on hydrocortisone 10-0-5 mg and thyroxine 25 μg/d, with resolution of symptoms and electrolyte normalization. A challenge trial of cortisol discontinuation led to symptomatic relapse.

Conclusions: Clinical cortisol deficiency with normal baseline serum cortisol can be defined as subthreshold condition. Concurrent ACTH measurements and stimulation tests are necessary to unmask the problem. The definition should not contest current diagnostic cut-offs or the principle of quaternary prevention.