Endocrine Abstracts

Background: Assessment of hypothalamic–pituitary adrenal axis in patients with schizophrenia is complex, as it involves both the disease process and antipsychotic medications. We present a case of a patient on long term clozapine with a concomitant pituitary adenoma who presented discordant responses to adrenal stimulation.

Case: A 38-year old male was referred with chronic symptoms of reduced libido and associated low testosterone levels. He was treated for paranoid schizophrenia with clozapine 100 mg q.am and 400 mg note for many years. On further assessment he was normally masculinized, with testes of normal size and texture and no galactorrhea. However, testosterone levels were confirmed low at 20 mg/dl with low gonadotropins (FSH 1.51 mIU/ml, LH 0.73 mIU/ml), normal prolactin 7.93 ng/ml, TSH 2.52 μIU/ml and fT₄ 0.68 ng/dl (normal 0.84–1.76). IGF-1 and morning cortisol levels were frankly low, at 26 ng/ml (normal range for age and sex 94–360) and 3.44 μg/dl respectively, making the diagnosis of panhypopituitarism. MRI of the sella showed a pituitary adenoma 10×10.7 mm. He was placed on hydrocortisone, thyroxine and testosterone replacement and underwent a successful endoscopic transphenoidal adenomectomy six months later. Stimulation with 1 μg tetracosactrin six months postoperatively showed a peak cortisol response of 11.7 μg/dl. Glucagon stimulation test also showed an inadequate peak cortisol response (9.32 μg/dl at 180′). At the same time, the responses of ACTH and cortisol to corticotropin-releasing hormone stimulation were normal, with a peak of 132 pg/ml at 15′ and 19.90 μg/dl at 30′ respectively. One year after surgery, morning cortisol levels were restored and hydrocortisone replacement was stopped. Repeat stimulation with 1 and 250 μg tetracosactrin and 1mg glucagon, showed peak cortisol responses of 16.0 at 30′, 21.60 at 60′ and 20.5 μg/dl at 180′, respectively. The patient remains GH, gonadotropin and TSH deficient.

Conclusions:

1) Clozapine may blunt glucagon-stimulated ACTH secretion

2) Currently employed dynamic tests of adrenal axis in patients with pituitary pathology in the presence of antipsychotic medications cannot accurately reflect true capacity for stress response).