Hypothalamic-Pituitary Axis in Non-Functioning Pituitary Adenomas: Focus on the Prevalence of Isolated Central Hypoadrenalism

Abstract

Introduction: Non-functioning pituitary adenomas (NFPA) account for about 40% of pituitary tumors. Pituitary deficiencies are present at diagnosis in 60-80% of NFPA, and, classically, growth hormone (GH) secretion is lost first, while adrenocorticotropic hormone is expected to disappear last. The aim of this study was to evaluate the incidence of multiple or isolated pituitary deficiencies in a large series of NFPA. Materials and Methods: We retrospectively analyzed data on 218 NFPA cases (59% females, 59% with macroadenomas, average age: 50.2 ± 17 years) followed up at our center from 1990 to 2013. At diagnosis all patients had a complete evaluation of pituitary function in basal conditions and provocative tests for the hypothalamic-pituitary-adrenal axis, while tests for GH deficiency (GHD) were carried out in 38%. Results: 52.3% of patients (65.6% of macroadenomas, 33.3% of microadenomas) presented at least 1 pituitary deficiency: isolated deficiency in 29.8%, multiple deficiencies in 30% and panhypopituitarism in 9%. Isolated deficiencies were hypogonadism in 11.5% of patients (8% in micro-, 14% in macroadenomas), hypoadrenalism in 10.1% (14% in micro-, 7% in macroadenomas) and GHD in 8.3% (8.9% in micro-, 7.8% in macroadenomas). About 30% of microadenomas had at least 1 pituitary deficiency at diagnosis, independently of tumor localization within the sellar region. Conclusions: The presence of isolated hypoadrenalism suggests that the order of appearance of hypopituitarism does not always follow the one expected. Given the relatively high prevalence of isolated hypoadrenalism even in microadenomas, we suggest a full assessment of basal and dynamic pituitary function in all NFPA regardless of tumor size.

Recovery of adrenal function after chronic secondary adrenal insufficiency in patients with hypopituitarism

“…To our knowledge, this is the first study to describe continued recovery of HPA function after long‐standing SAI in patients with pituitary disorders. Previous studies have shown that 10–32% of patients with sellar masses have an associated SAI at presentation . In particular, the risk of SAI is higher in patients with craniopharyngiomas and hypophysitis such that 24–62% of patients with craniopharyngiomas and up to 50% of patients with hypophysitis have SAI at presentation .…”

“…Primary diagnoses were NFA (23), prolactinoma (PRLoma) (5), craniopharyngioma (5), GH-producing adenoma (4), hypophysitis (5), Rathke's Cleft cyst (3), empty sella (2), osteolipoma (1), idiopathic (1), oncocytoma (1) and pituitary epithelial neoplasm (1). Of these patients, 11 had conservative management with no surgical intervention, whereas the remaining 40 patients underwent the following procedures: transsphenoidal resection of tumour (35), stereotactic radiation therapy (3), pituitary biopsy (1), craniotomy (1), drainage of pituitary cyst (1), transcortical transventricular endoscopic fenestration with subtotal resection (1) and yttrium treatment (1). The median duration of glucocorticoid therapy prior to discontinuation (if possible) was 37 months (range: 8-112).…”

“…Their median cortisol at presentation was 53 nM (range: 0-244). The primary diagnoses in this group were as follows: NFA (19), PRLoma (3), GH-producing adenoma (3), craniopharyngioma (5), hypophysitis (3), Rathke's Cleft cyst (3), empty sella (2), osteolipoma (1), idiopathic (1), oncocytoma (1) and pituitary epithelial neoplasm (1). Thirty-two patients underwent an intervention, including transsphenoidal surgical resection (30), transcortical transventricular endoscopic fenestration with subtotal resection (1), and yttrium treatment (1).…”

“…Secondary adrenal insufficiency (SAI) as a result of the disruption of the hypothalamic–pituitary–adrenal (HPA) axis commonly occurs in patients with pituitary disorders. Though usually in combination with multiple hormonal deficiencies, SAI can be isolated in around 10% of cases . There is evidence that the HPA axis can recover in up to 47% patients after surgical decompression of sellar masses .…”

“…Though usually in combination with multiple hormonal deficiencies, SAI can be isolated in around 10% of cases. 1 There is evidence that the HPA axis can recover in up to 47% patients after surgical decompression of sellar masses. [2][3][4] Furthermore, continued postoperative recovery of the HPA axis leading to resolution of SAI has previously been demonstrated up to 12 months after transsphenoidal surgery.…”