Relationship between disease duration and predominant orbital T cell subset in Graves' ophthalmopathy.

We sought to determine whether the predominant orbital T helper (T(H)) cell subset in orbital T cell clones established from patients with Graves' ophthalmopathy (GO) might be related to disease duration. A total of 117 clones were established from orbital adipose/connective tissues of 6 GO patients, and cytokine production was measured in 57 CD3+CD4+ clones. T(H)1-type clones were predominant in cultures from patients with recent onset (<2 yr) Graves' hyperthyroidism (n = 44; TH1/TH0/TH2 = 57/29/14%) or GO (n = 53 clones; TH1/TH0/TH2 = 47/30/23%). In contrast, TH2-type clones predominated in cultures from patients with more remote onset (>2 yr) hyperthyroidism (n = 13; TH1/TH0/TH2 = 0/31/69%; P < 0.005) or GO (n = 4; TH1/TH0/TH2 = 0/25/75%; P = 0.05). In addition, we established T cell clones from 1 TH1-dominant patient with recent-onset thyroid and eye disease using either IL-2 (12.5 ng/mL) alone or IL-2 plus IL-4 (5 ng/mL) and found no shift toward recovery of TH2-type clones in the latter. In conclusion, although the CD3+CD4+ clones characterized were not necessarily tissue antigen specific, our findings suggest that cell-mediated (TH1-type) immune reactions may predominate in the orbit in early GO, whereas humoral immunity (TH2-type) might play the greater role in later stages of the disease.

Tension pneumocranium, a rare complication of transsphenoidal pituitary surgery: Mayo Clinic experience 1976-1998.

We describe four cases of symptomatic pneumocranium, a rare, potentially life-threatening complication of transsphenoidal pituitary surgery. Symptomatic pneumocranium manifested as impaired mental status, headaches, and grand mal seizures, early in the postoperative course after transsphenoidal pituitary surgery. Furthermore, a Cushing response, including systemic hypertension and bradycardia (secondary to intracranial hypertension) was seen, which has not been previously described in association with symptomatic pneumocranium. We describe a previously unreported risk factor for tension pneumocranium, untreated obstructive sleep apnea. Other factors predisposing to tension pneumocranium in our patients included: cerebrospinal fluid leaks, postoperative positive-pressure mask ventilation, large pituitary tumors, and intraoperative lumbar drainage catheters. Surgical drainage of the pneumocranium and repair of any coexistent cerebrospinal fluid leak markedly improved neurologic status. Symptomatic pneumocranium occurring early in the postoperative course after transsphenoidal pituitary surgery is rare, but prompt recognition and treatment of this condition can be life-saving.

Cushing syndrome due to ectopic adrenocorticotropic hormone secretion.

Cushing syndrome (CS) caused by ectopic adrenocorticotropic hormone (ACTH) production (EA) poses major challenges diagnostically by mimicking the pituitary-dependent form of CS and therapeutically by producing severe, life-threatening hypercortisolemia. This retrospective follow-up study describes the clinical characteristics and course of EA in a large referral center. Computer-based cross-index codes for EA, CS, and bilateral adrenalectomy were used to identify patients treated at the Mayo Clinic between 1956 and 1998. EA was confirmed in 106 patients. Gender distribution showed a slight female predominance (61:45). Bronchial carcinoid was the most frequent cause of EA (25%), followed by islet cell cancer (16%), small-cell lung carcinoma (11%), medullary thyroid cancer (8%), disseminated neuroendocrine tumor of unknown primary source (7%), thymic carcinoid (5%), pheochromocytoma (3%), disseminated gastrointestinal carcinoid (1%), and other tumors (8%). No tumor was found in 16% of patients. Altogether, 28 patients were managed medically, and the others underwent curative tumor resection (13 patients) or bilateral adrenalectomy (65 patients). Surgically treated patients had longer survival, but this was most likely affected by treatment bias. The diagnoses of CS and ACTH-secreting neoplasm were usually concurrent, although, there were remarkable cases in which the two conditions were diagnosed several years apart. Curative resection of the tumor producing EA was possible in a small proportion of patients (12%). When curative resection is not possible, patients who are reasonable surgical candidates are likely to benefit from adrenalectomy. Additional experience with bilateral laparoscopic adrenalectomy should increase the number of patients who benefit from adrenal-directed surgery.