Low Plasma Oxytocin Levels and Increased Psychopathology in Hypopituitary Men With Diabetes Insipidus.

CONTEXT: Oxytocin (OT) and vasopressin share anatomical pathways of synthesis and secretion, and patients with central diabetes insipidus (CDI) presumably are at risk for OT deficiency. However, an OT-deficient state in hypopituitary patients has not been established. OBJECTIVES: We hypothesized that men with CDI compared to patients with similar anterior pituitary deficiencies (APD) but no CDI and healthy controls (HC) of similar age and body mass index, would have lower plasma OT levels, associated with increased psychopathology. DESIGN: Cross-sectional. SETTING: Clinical research center. PARTICIPANTS: Sixty-two men (20 CDI, 20 APD, 22 HC), age 18 to 60 years. INTERVENTIONS: Frequent sampling of blood every 5 minutes for OT over 1 hour and validated questionnaires to assess psychopathology. MAIN OUTCOMES: Pooled plasma OT levels; depressive, anxiety, and alexithymia symptoms; and quality of life. RESULTS: The mean 1-hour pool of fasting OT levels was lower in CDI compared with APD and HC (P = 0.02 and P = 0.009, respectively), with no differences between APD and HC (P = 0.78). Symptoms of depression, anxiety, and alexithymia were more pronounced in CDI than in HC (P = 0.001, P = 0.004, and P = 0.02, respectively). Although CDI and APD reported worse physical health compared with HC (P = 0.001 and P = 0.005) with no differences between APD and CDI, only CDI reported worse mental health compared with HC (P = 0.009). CONCLUSIONS: We have demonstrated low plasma OT levels and increased psychopathology in hypopituitary men with CDI, suggestive of a possible OT-deficient state. Larger studies of both sexes are required to confirm these findings and clinically characterize hypopituitary patients with OT deficiency.

Hypopituitarism After Cranial Irradiation for Meningiomas: A Single-Institution Experience.

PURPOSE: Patients undergoing cranial irradiation are at high risk for development of subsequent pituitary deficiencies. Patients with meningiomas can expect to live many years after treatment and are therefore particularly vulnerable to long-term sequalae of radiation therapy (RT). The purpose of this study was to determine the rates and timing of onset of pituitary dysfunction across each hypothalamic-pituitary axis in patients with meningiomas in the sellar region. METHODS AND MATERIALS: Data from 74 patients with meningiomas in the sellar or perisellar region who underwent RT between 2001 and 2017 at a single academic center were analyzed. Dose-volume histograms were generated to determine the dose of radiation to the pituitary gland. Pituitary function tests were evaluated before and after completion of RT. RESULTS: There was a 20% risk for new hypopituitarism across any hypothalamic-pituitary axis after RT at a median follow-up of 43 months. Identified rates of dysfunction across each axis were 24% for thyroid and adrenal, 19% for growth hormone, and 10% for gonadal. Median time to develop deficiencies ranged from 11 months for growth hormone deficiency to 32 months for adrenal insufficiency. Deficiencies were likely to be correlated, with increased risk for thyroid dysfunction in patients with adrenal, gonadal, or prolactin deficiencies (P < .05). On univariate analysis, mean dose to the pituitary gland and male sex were associated with increased risk for post-RT thyroid deficiency (P = .01 and P = .004, respectively). There was no difference in rates of hypothyroidism after protons compared with photons (P = .14). CONCLUSIONS: Cranial irradiation for sellar meningiomas carries a risk for subsequent hypopituitarism that appears to be dose dependent and may occur years after completion of RT. Growth hormone deficiency and gonadal dysfunction were likely underestimated here secondary to a lack of routine testing. Given the favorable tumor prognosis in this patient population, early and long-term endocrine follow-up is warranted.

TWO SYNCHRONOUS PITUITARY ADENOMAS CAUSING CUSHING DISEASE AND ACROMEGALY.

OBJECTIVE: To report the first case of 2 synchronous pituitary adenomas, 1 corticotroph and 1 somatotroph, with distinct molecular lineages confirmed by differential hormone and S-100 protein expression. METHODS: A case report followed by a literature review are presented. RESULTS: A 68-year-old woman presented for evaluation of resistant hypertension. Biochemical testing demonstrated adrenocorticotropic hormone (ACTH)-dependent hypercortisolemia and growth hormone (GH) excess. Pituitary magnetic resonance imaging (MRI) revealed a 2 cm left sellar lesion consistent with a pituitary macroadenoma. The patient therefore underwent transsphenoidal surgery for a presumed cosecreting ACTH and GH macroadenoma. Tumor immunohistochemical staining (IHC) was positive for ACTH, but negative for GH. Postoperative biochemical testing confirmed remission from Cushing disease, but the insulin-like growth factor 1 (IGF-1) level remained elevated. Postoperative MRI demonstrated a small right sellar lesion that, in retrospect, had been present on the preoperative MRI. Resection of the right lesion confirmed a GH-secreting adenoma with negative ACTH staining. After the second surgery, the IGF-1 level normalized and blood pressure improved. Further pathologic examination of both surgical specimens demonstrated differential expression of S-100 protein, a folliculostellate cell marker. Reverse transcription polymerase chain reaction of messenger ribonucleic acid from the left sellar lesion was positive for ACTH and negative for GH, confirming the IHC results. Germline mutations in genes known to be associated with pituitary adenoma syndromes (MEN1, CDC73, CDKN1A, CDKN1B, CDKN2B, CDKN2C, and AIP) were not detected. CONCLUSION: Although the pathogenesis of synchronous pituitary adenomas has not been fully elucidated, this case report suggests that they can have distinct molecular lineages.