Effect of Distance from Target on Hypopituitarism After Stereotactic Radiosurgery for Pituitary Adenomas

IntroductionDelayed hypopituitarism is the most common complication after stereotactic radiosurgery (SRS) for pituitary adenomas. The aim of this study was to investigate the relationship between the distance from the hypothalamic-pituitary axis to the treatment target and anterior pituitary function preservation after SRS. MethodsBetween 2007 and 2020, consecutive adult patients who underwent single-session SRS for pituitary adenomas with ³6 months of follow-up were included. Distance measurements between hypothalamic-pituitary axis structures and the SRS target volume were quantified on MRI. The primary outcome was anterior pituitary function preservation. Outcomes were compared using multivariable regression and area under the receiver operator characteristic curve (AUROC) analyses. ResultsThe study cohort comprised 224 patients, who were categorized by preservation (n=168) and no preservation (n=56) of anterior pituitary function after SRS. Independent predictors of anterior pituitary function preservation were a greater distance between the center of the pituitary gland and center of the SRS target (OR=1.101 [1.000–1.213], p=0.050), and a shorter clinical follow-up duration (OR=0.985 [0.977–0.993], p<0.0001). The adjusted AUROC for the distance from the center of the pituitary gland and center of the SRS target in predicting anterior pituitary function preservation was 0.595. The sensitivity, specificity, positive predictive value and negative predictive value in predicting anterior pituitary function preservation at the optimal cut-off distance of 15mm were 30.0%, 88.0%, 89.9% and 26.2%, respectively.ConclusionsGreater distance between the normal pituitary gland and the SRS target is associated with anterior pituitary function preservation and increasing this distance should be a goal of adenoma resection. Larger prospective, multi-center studies are necessary to corroborate this finding and establish the effects of distance on hypopituitarism after SRS for pituitary adenomas.

Idiopathic combined adrenocorticotropin and growth hormone deficiency mimicking chronic fatigue syndrome

A 42-year-old man who had suffered from severe fatigue for 5 years was diagnosed as having chronic fatigue syndrome (CFS) and fibromyalgia. Endocrinological workup using combined anterior pituitary function tests showed that the patient had adrenocorticotropin hormone (ACTH) deficiency, with a normal pituitary MRI. Treatment with a physiologic dose of oral hydrocortisone replacement physically ameliorated his general fatigue. A secondary workup using a growth hormone-releasing peptide-2 test revealed that he also had growth hormone (GH) deficiency, and GH replacement therapy was started. His muscle pain and depression were improved by the therapy. Here, we present a rare case of combined deficiency of ACTH and GH in a middle-aged man with severe general fatigue. This case report aims to raise awareness of combined deficiency of ACTH and GH as a differential diagnosis of CFS and its mimics.

The primary empty Sella: An endocrine study on 36 cases

Introduction: The term primary empty sella (PES) makes reference to the herniation of the subarachnoid space within the sella turcica in patients with no history of pituitary tumor, surgery or radiotherapy. Materials and Methods: We studied 36 patients; 27 females and 9 males. The mean age at diagnosis was 50, 4 years [21-80 years]. Most diagnoses were made by magnetic resonance imaging (n = 32). The anterior pituitary function was evaluated by basal hormonal measurements. Then, we had compared two groups of patients: G1(n=17), who had a pituitary disorder, and G2 (n=10), patients without hormonal disease, in order to determine risk factors for endocrine dysregulation in PES. Results: The reasons for ordering pituitary scans were: headaches (65%), visual disturbances (32%) and neurological symptoms in 8% of cases. Sixty-six point five per cent of women were multiparous. Diabetes, obesity and hypertension were found in 19.45 %, 11 % and 19.45 % of the studied population respectively. Hyperprolactinemia was present in 17.24 % of patients. Fifty-five percent of our patients had some degree of hypopituitarism. We didn’t find any correlation in our study, between pituitary insufficiency and age, gender, weight, parity nor post-partum hemorrhage. Failure of lactation was significantly associated with a hormonal disorder. On the other hand, headache was negatively correlated with hormonal effects in PES. Conclusion: PES was most commonly found in middle-aged multiparous women. In most patients, PES is a heterogeneous condition that ranges from hypopituitarism to various degrees of isolated GH deficiency, and which needs careful endocrine assessment, treatment and follow-up.

Two Cases of Pembrolizumab-Induced Secondary Adrenal Insufficiency

Title: Two cases of pembrolizumab-induced secondary adrenal insufficiency Background: Although few cases regarding pembrolizumab-induced secondary adrenal insufficiency were reported, it has recently been published that significantly higher prevalence of human leucocyte antigen (HLA)-DR15, B52, and Cw12 was revealed in 11 Japanese patients with immune checkpoint inhibitor-induced secondary adrenal insufficiency as compared with healthy controls and DR15 might be a predictive marker. This is based on the evidence that DR15 has associations with IL-17-mediated autoimmune disease such as Hashimoto’s thyroiditis, and that anti-programmed death 1 (PD-1) inhibitors activate the Th1 and Th17 pathways. We here introduce two Japanese patients with pembrolizumab-induced secondary adrenal insufficiency from a viewpoint of their HLA typing test results. Clinical Case: Case 1. A 52-year old male diagnosed with stage IV lung cancer (squamous non-small cell lung cancer) was treated with chemotherapy consisting of carboplatin, nab-paclitaxel, and pembrolizumab. Six days after the fourth cycle of pembrolizumab, he suffered from hypoglycemia and hyponatremia. Endocrinological examination findings showed ACTH and cortisol deficiency throughout the day, after which a diagnosis of secondary adrenal insufficiency was made based on no response shown in insulin tolerance, anterior pituitary function, and rapid ACTH stimulation tests. Pituitary cell antibody-1 was negative, and no evidence of a swollen/atrophied pituitary gland or space occupying lesion was observed in magnetic resonance imaging (MRI) results. Furthermore, Hashimoto’s thyroiditis was suspected based on anti-thyroid peroxidase antibody positivity. HLA typing test results highly corresponded with the reported results (A24, B52, Cw12, DR4, DR15). Case 2. A 70-year old male was treated with pembrolizumab for recurrence of lung squamous cell carcinoma (stage IV). Two weeks after completion of five cycles, severe diarrhea occurred, suspected to be a side effect of pembrolizumab, which was relieved with temporary use of prednisolone. However, diarrhea recured accompanied with a high fever, eosinophilia, and acute hyponatremia. Based on results showing deficiency of ACTH and cortisol, adrenal insufficiency was suspected. Anterior pituitary function and rapid ACTH stimulation test results supported that diagnosis, while pituitary cell antibody-1 was negative and MRI findings were not remarkable. Notably, completely different HLA typing test results were observed. Conclusion: Similar to the previous report, HLA-A24, B52, Cw12, DR4, and DR15 were found in case 1, whereas all subtypes including HLA-DR15 were lacking in case 2. We think that it should not be given low priority for cases lacking DR15 and the possibility of an association with IL-17 in such cases is required in feature study.

OTHR-09. CENTRAL DIABETES INSIPIDUS: A RARE UNREPORTED SIDE EFFECT OF TEMOZOLOMIDE IN PEDIATRICS

Temozolomide is a chemotherapeutic agent commonly used in the treatment of central nervous system tumors. While there are case reports of temozolomide associated central diabetes insipidus (CDI) in adults, this has not been reported in children. We describe the first case of temozolomide associated CDI in a pediatric patient. The patient was a previously healthy 12yr old male diagnosed with anaplastic astroblastoma. He underwent gross total resection of the lesion and was subsequently treated with focal radiation therapy and concurrent temozolomide. On day 21 of therapy he developed thrombocytopenia, severe polyuria and polydipsia. Temozolomide was held and he underwent a preliminary evaluation for CDI. Initial laboratory findings were concerning for CDI, and he was admitted for further work-up and to assess the need for desmopressin. Additional laboratory tests demonstrated normal anterior pituitary function and his serum sodium normalized when allowed to drink to thirst, mitigating the need for desmopressin. Temozolomide was not restarted and the symptoms of polyuria and polydipsia resolved and did not recur. Upon review, the tumor did not involve the pituitary or hypothalamus. Additionally, these areas were not involved in the irradiation field. CDI is a rare but clinically significant side effect of temozolomide, reported in adults. Given this is the first report of CDI secondary to temozolomide in a pediatric patient, we speculate that this is likely under-recognized in children. Prompt recognition and treatment is necessary to prevent severe sequelae of hypernatremia.

Late diagnosis of isolated central diabetes insipidus secondary to congenital toxoplasmosis—case report

ABSTRACT Congenital toxoplasmosis is an uncommon infection. Hypothalamic/pituitary involvement leading to isolated central diabetes insipidus is extremely rare. Making a correct diagnosis of this condition, albeit challenging, is crucial for adequate management. We present a 54-year-old female who developed central diabetes insipidus as a complication of congenital toxoplasmosis. She had polydipsia and hypernatraemia on presentation and responded to intranasal desmopressin with normalization of above-mentioned findings. Magnetic resonance imaging and cranial X-ray’s showed pronounced intracranial calcifications in both choroid plexuses. Thyroid function tests, serum cortisol level and anterior pituitary function were all normal. To the best of our knowledge, this is the first reported case of isolated diabetes insipidus due to congenital toxoplasmosis in literature diagnosed late in adulthood and gives an insight into the challenges of diagnosing central diabetes insipidus and the hypothalamic/pituitary involvement in cases of congenital toxoplasmosis.

A Case Series of Patients with Isolated IgG4-related Hypophysitis Treated with Rituximab

Context The acute presentation of immunoglobulin G4 (IgG4)-related hypophysitis can be indistinguishable from other forms of acute hypophysitis, and histology remains the diagnostic gold standard. The high recurrence rate necessitates long-term immunosuppressive therapy. Rituximab (RTX) has been shown to be effective in systemic IgG4-related disease (IgG4-RD), but experience with isolated pituitary involvement remains limited. Case Description We report 3 female patients with MRI findings suggestive of hypophysitis. All patients underwent transsphenoidal biopsy and fulfilled diagnostic criteria for IgG4-related hypophysitis. Treatment with glucocorticoids (GCs) resulted in good therapeutic response in Patients 1 and 2, but the disease recurred on tapering doses of GCs. GC treatment led to emotional lability in Patient 3, necessitating a dose reduction. All 3 patients received RTX and Patients 2 and 3 received further courses of treatment when symptoms returned and B-cells repopulated. Patient 3 did not receive RTX until 12 months from the onset of symptoms. Patient 1 was not able to have further RTX treatments due to an allergic reaction when receiving the second dose. Rituximab treatment resulted in sustained remission and full recovery of anterior pituitary function in Patients 1 and 2, with complete resolution of pituitary enlargement. By contrast, Patient 3 only showed a symptomatic response following RTX treatment, but pituitary enlargement and hypofunction persisted. Conclusion Rituximab treatment for IgG4-related hypophysitis resulted in sustained remission in 2 patients treated early in the disease process but only achieved partial response in a patient with chronic disease, suggesting that early therapeutic intervention may be crucial in order to avoid irreversible changes.