MON-253 A Rare Case of Pituitary Aspergillosis Diagnosed by CSF PCR in an Immunocompetent Patient with Headaches and Photophobia

Abstract Background: Pituitary aspergillosis is a rare infection usually found in the immunocompromised population. It is oftentimes mistaken for a pituitary adenoma based on similar clinical presentation and characteristic findings on MRI. Most cases require removal of the pituitary mass in order to make a diagnosis. Here we present the case of an immunocompetent patient with headaches and photophobia diagnosed with pituitary aspergillosis by CSF PCR and treated medically with voriconazole. Clinical Case: A 40-year-old woman with a questionable history of Brucellosis presented with a 3 month history of headaches along with 2 days of nausea and vomiting. Vital signs were notable for intermittent hypotension but were otherwise within normal limits. Physical exam was notable for tenderness at the left temporal region, diaphoresis and photophobia. Patient was otherwise alert and oriented and had no visual field deficits or extraocular muscle dysfunction. Patient was found to have central adrenal insufficiency with undetectable AM cortisol (<0.5 mcg/dL, n 3.7-19.4 mcg/dL), inappropriately normal ACTH (7 pg/mL, n 6-58 pg/mL) and central hypothyroidism with low TSH (0.057 mcIU/mL, n 0.358-3.8 mcIU/mL) and low free T4 (0.48 ng/dL, n 0.76-1.46 ng/dL). Patient initially presented with hyponatremia (Na 119 mmol/L, n 137-145 mmol/L) likely secondary to central adrenal insufficiency and central hypothyroidism. Gadolinium-enhanced pituitary MRI showed a heterogeneous 1.8 cm pituitary mass with rim enhancement concerning for hypophysitis. Patient was started on stress-dose steroids with IV hydrocortisone 100 mg IV q8h, levothyroxine 50 mcg PO daily and empiric antibiotic therapy with ceftriaxone, doxycycline and rifampin due to suspicion for neurobrucellosis. Lumbar puncture was obtained showing low glucose (39 mg/dL, n 40-70 mg/dL), normal protein (47 mg/dL, n 12-60 mg/dL) and an elevated white count (WBC 9/mcL, n 0-5/mcL) with lymphocyte predominance (97% lymphocytes, n 40-80%). Blood and CSF cultures showed no growth at 2 weeks. CSF was sent for multiplex PCR which came back positive for Aspergillus. Patient was discharged with voriconazole 300 mg PO BID for 1 year, levothyroxine 75 mcg PO daily and hydrocortisone 10 mg PO Qam and 5 mg PO Qpm. Three months later, repeat MRI showed resolution of the pituitary mass and patient felt well without headaches, nausea or vomiting. Conclusion: This case demonstrates an atypical example of pituitary aspergillosis diagnosed without pituitary mass biopsy and treated medically with voriconazole. It demonstrates the possible role of CSF PCR to diagnose the condition and guide antifungal treatment.

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SUN-298 Spectrum of Imaging in Immune Checkpoint Inhibitor Induced Hypophysitis

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.1584 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Zoe Quandt ◽

Stephanie Kim ◽

Javier Villanueva-Meyer ◽

Catherine Coupe ◽

J Blake Tyrrell ◽

...

Keyword(s):

Family History ◽

Adrenal Insufficiency ◽

Immune Checkpoint ◽

Checkpoint Inhibitors ◽

Empty Sella ◽

Central Hypothyroidism ◽

History Of ◽

Pituitary Enlargement ◽

Central Adrenal Insufficiency

Abstract Background: Hypophysitis (HP) is a known immune related adverse event of immune checkpoint inhibitors (CPIs), commonly associated with CTLA-4 inhibitors and rarely with PD-1/PD-L1 inhibitors. Prior studies of MRIs at HP diagnosis noted pituitary enlargement with resolution within a few weeks. In this study, we examine MRI changes in patients with CPI-induced HP. Methods: Subjects with biochemical evidence of central hypothyroidism or central adrenal insufficiency and MRIs were reviewed by endocrinology and neuroradiology. MRIs were classified relative to HP diagnosis: baseline (at least 21 days prior), diagnosis (within 21 days), and follow up (over 21 days). Patient characteristics included age at CPI initiation, sex, race/ethnicity, personal and family history of autoimmunity, type of cancer and CPI. Results: Twenty-six subjects met the inclusion criteria. The mean age was 59 years; 62% were male and 86% were non-Hispanic white. Nineteen percent had a personal history and 31% a family history of autoimmunity. Fifty percent had melanoma. At HP diagnosis, 46% were on PD-1/PD-L1 inhibitors, 42% were on combination PD-1/CTLA-4 inhibitors and 12% were on CTLA-4 inhibitors. Median time from CPI initiation to HP diagnosis was 95 days. Time to HP was shorter on a CTLA-4 inhibitor combination or monotherapy (median 82 days) compared to a PD-1/PD-L1 inhibitor monotherapy (median 220 days; Wilcoxon rank sum, p <0.01). Central adrenal insufficiency was present in all patients not yet on steroids. Central hypothyroidism was common (10/19) in those without primary thyroid disease and was not associated with type of CPI (Fisher’s exact, p=0.18). Thirteen subjects had baseline MRIs, 18 had MRIs at HP diagnosis and 13 had MRIs in the follow up period. Baseline MRIs were normal in 12/13; one subject had an enlarged pituitary. At diagnosis, 10 had an enlarged pituitary, 7 a normal pituitary and 1 a partially empty sella. CTLA-4 inhibitor exposure was associated with pituitary enlargement at diagnosis: 9/11 compared to 1/7 on PD-1/PD-L1 inhibitor (Fisher’s exact, p <0.04). Of the subjects who had follow-up MRIs, 3 had an enlarged pituitary, 7 a normal pituitary and 3 a partially empty sella. Follow up imaging did not differ between treatment types (Fisher’s exact, p >0.05). Timing of MRI was significantly associated with pituitary appearance (Fisher’s exact, p <0.01). Conclusion: The MRI appearance of HP presents as a spectrum, from a partially empty sella, normal pituitary to an enlarged pituitary. HP diagnosed in the setting of CTLA-4 inhibitor treatment occurs earlier and is more likely to induce an enlarged pituitary gland compared to PD-1/PD-L1 monotherapy, which occurs later and is associated with a normal appearing MRI at diagnosis. This suggests that the pathogenesis of HP following CPI exposure may vary depending on the type of CPI.

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Immune checkpoint inhibitor related hypophysitis: diagnostic criteria and recovery patterns

Endocrine Related Cancer ◽

10.1530/erc-20-0513 ◽

2021 ◽

Author(s):

Ha Nguyen ◽

Komal Shah ◽

Steven G Waguespack ◽

Mimi I Hu ◽

Mouhammed Amir Habra ◽

...

Keyword(s):

Adrenal Insufficiency ◽

Diagnostic Criteria ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitor ◽

Checkpoint Inhibitor ◽

High Dose ◽

Central Hypothyroidism ◽

Central Adrenal Insufficiency ◽

Mri Changes

Data on the diagnosis, natural course and management of immune checkpoint inhibitor (ICI) related hypophysitis (irH) are limited. We propose this study to validate the diagnostic criteria, describe characteristics and hormonal recovery and investigate factors associated with occurrence and recovery of irH. A retrospective study including patients with suspected irH at the University of Texas MD Anderson Cancer Center from 5/2003 to 8/2017 was conducted. IrH was defined as: (1) ACTH or TSH deficiency plus MRI changes or (2) ACTH and TSH deficiencies plus headache/fatigue in the absence of MRI findings. We found that of 83 patients followed for a median of 1.75 years (range 0.6-3), the proposed criteria used at initial evaluation accurately identified 61/62 (98%) irH cases. In the irH group (n=62), the most common presentation were headache (60%), fatigue (66%), central hypothyroidism (94%), central adrenal insufficiency (69%) and MRI changes (77%). Compared with non-Ipilimumab (Ipi) regimens, Ipi has a stronger association with irH occurrence (p=0.004) and a shorter time to irH development (p<0.01). Thyroid, gonadal and adrenal axis recovery occurred in 24%, 58% and 0% patients, respectively. High dose steroids (HDS) or ICI discontinuation were not associated with hormonal recovery. In the non-irH group (n=19), one patient had isolated central hypothyroidism and 6 had isolated central adrenal insufficiency. All remained on hormone therapy at last follow up. We propose a strict definition of irH that identifies the vast majority of patients. HDS and ICI discontinuation is not always beneficial. Long term follow up to assess recovery is needed.

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A Case of Rathke’s Cleft Cyst Associated with Transient Central Adrenal Insufficiency and Masked Diabetes Insipidus

Case Reports in Endocrinology ◽

10.1155/2014/693294 ◽

2014 ◽

Vol 2014 ◽

pp. 1-6

Author(s):

Masahiro Asakawa ◽

Rina Chin ◽

Yoshihiro Niitsu ◽

Tetsuo Sekine ◽

Arisa Niwa ◽

...

Keyword(s):

Diabetes Insipidus ◽

Adrenal Insufficiency ◽

Optic Chiasm ◽

Nasal Administration ◽

Rathke’S Cleft Cyst ◽

Rathke's Cleft Cyst ◽

Pituitary Mass ◽

Silent Thyroiditis ◽

Central Adrenal Insufficiency ◽

Rathke's Cleft

A 73-year-old woman admitted to our hospital because of headache, poor appetite, malaise, weight loss, and vomiting was found to have central adrenal insufficiency and thyrotoxicosis due to silent thyroiditis. Polyuria developed after replacement with glucocorticoid (masked diabetes insipidus), which was controlled with nasal administration of desmopressin. Magnetic resonance imaging of the brain showed a large cystic pituitary mass (18 × 18 × 12 mm) extending suprasellarly to the optic chiasm. Transsphenoidal surgery revealed that the pituitary tumor was Rathke’s cleft cyst. Following surgery, replacement with neither glucocorticoid nor desmopressin was needed any more. Therefore, it is suggested that Rathke’s cleft cyst is responsible for the masked diabetes insipidus and the central insufficiency. Furthermore, it is speculated that thyrotoxicosis with painless thyroiditis might induce changes from subclinical adrenal insufficiency to transiently overt insufficiency.

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Case Series: Four Cases of Anorexia Nervosa Concomitant with Central Adrenal Insufficiency

10.21203/rs.3.rs-589860/v1 ◽

2021 ◽

Author(s):

Sunao Matsubayashi ◽

Madoka Tanaka ◽

Takeshi Hara

Keyword(s):

Anorexia Nervosa ◽

Adrenal Insufficiency ◽

Case Series ◽

Addison’S Disease ◽

Tolerance Test ◽

Addison's Disease ◽

Level Of Evidence ◽

Insulin Tolerance ◽

History Of ◽

Central Adrenal Insufficiency

Abstract Objective: Widespread attention has been paid to the misdiagnosis of life-threatening Addison's disease as anorexia nervosa. However, there are no reports on the possible comorbidity of Addison's disease and other adrenal insufficiencies with anorexia nervosa.Methods: A case-series presentation of anorexia nervosa concomitant with central adrenal insufficiency.Results: Four anorexia nervosa patients (21-35 years old, all females) complained of severe fatigue during their treatment. After a thorough examination of the hypothalamus-pituitary-adrenal axis using stimulation with a rapid adenocorticotropic hormone test of 250-µg Cortrosyn®, a corticotropin-releasing hormone test, and an insulin tolerance test, central adrenal insufficiency was diagnosed. Two of the four patients had a history of exogenous steroids for their history of comorbidity. One of the residual two patient had Rathke’s cleft cyst. After the initiation of hydrocortisone replacement the patient's fatigue symptoms improved and they　were able to return to school and their workplace. In some cases, their weight obsession was reduced after the initiation of hydrocortisone replacement.Conclusion: Anorexia nervosa may be concomitant with central adrenal insufficiency partly in relation to exogenous steroids used for their history of comorbidity, which needs to be kept in mind when treating such patients.Level of EvidenceLevel V, descriptive study.

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Stuck at the Checkpoint: Pembrolizumab Induced Hypophysitis With ‘Normal’ Cosyntropin Response

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.1246 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A611-A611

Author(s):

Elnaz Kasiri ◽

Richard W Pinsker ◽

Marina Ravich ◽

Bijal Patel

Keyword(s):

Lung Adenocarcinoma ◽

Adrenal Insufficiency ◽

Cortisol Level ◽

Checkpoint Inhibitor ◽

Checkpoint Inhibitors ◽

Empty Sella ◽

Free T4 ◽

Advanced Malignancy ◽

Breath Sounds ◽

Central Adrenal Insufficiency

Abstract Introduction: Pembrolizumab is an immune checkpoint inhibitor (ICI) that blocks programmed cell death receptor 1 (PD-1) and is indicated in treatment of malignancies including lung adenocarcinoma and melanoma. Anti-PD-1 therapies are responsible for immune related adverse events including endocrine dysfunction. Here we present a case of Pembrolizumab induced hypophysitis causing central adrenal insufficiency apparently missed by a 250 mcg cosyntropin test. Clinical Case: A 68 year old female with history of COPD and stage 4 lung adenocarcinoma with bone metastases presented to the ED with hypotension during her 14th cycle of treatment with Pembrolizumab. Other symptoms included fatigue and anorexia for about 4 weeks. She denied vomiting, diarrhea, bleeding episodes or chronic steroid use. On exam, patient was obese and pale appearing, with decreased bilateral breath sounds without edema. Random cortisol on admission at 4:44 pm was 6.9 ug/dl, ACTH - was in process, Na was 135 (137 - 145 mEq/L) and K was 3.7 (3.5 - 5.1 mEq/L). A 250 mcg cosyntropin stimulation test resulted in 30 min cortisol level of 22.5 µg/dL and 60 min cortisol level of 34 µg/dL. Patient was treated with fluids, salt tabs and eventually midodrine, however BP remained borderline low. On day 5, the patient was started on IV methylprednisolone 40 mg Q8 hrs for COPD exacerbation. A few days later pre-steroid ACTH was reported as <5 pg/ml (6-50 pg/ml) which prompted further workup for hypopituitarism. LH and FSH levels were inappropriately low for a postmenopausal female at 0.2 and 2.6 mIU/ml respectively, Free T3 was 2.02 pg/ ml (2.77-5.27 pg/ml), free T4 was 1.07 ng/dl (0.80-2.20 ng/dl), and TSH was 0.67 uIU/ml (0.47-4.70 uIU/ml). MRI brain showed partially empty sella. Patient was diagnosed clinically with Pembrolizumab induced hypophysitis causing central adrenal insufficiency. Eventually, steroids were tapered to prednisone 5 mg daily maintenance dose and patient was discharged with stress dosing instructions. Conclusion: Diagnosis of adrenal insufficiency is challenging as advanced malignancy and adrenal insufficiency can cause similar symptoms. The finding of an empty sella here is a confounding factor. Checkpoint inhibitors are known to cause hypophysitis, thyroiditis and primary adrenal insufficiency, however incidence is <1%. We report a case of missed adrenal insufficiency by a falsely assuring cosyntropin test. Based on our experience, we conclude that when suspecting a diagnosis of checkpoint inhibitor induced adrenal insufficiency, we should start by checking random cortisol and ACTH value. A standard 250 mcg cosyntropin test should not be used solely to completely rule out this diagnosis.

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Pituitary Macroadenoma Masked by Iatrogenic Adrenal Insufficiency: A Diagnostic Blind Spot

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.305 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A151-A151

Author(s):

Ivy Hoi Yee Ng ◽

Elaine Yun Ning Cheung

Keyword(s):

Adrenal Insufficiency ◽

Hpa Axis ◽

Optic Chiasm ◽

Blind Spot ◽

Pituitary Hormones ◽

Pituitary Macroadenoma ◽

Pituitary Mass ◽

Blurred Vision ◽

Central Adrenal Insufficiency ◽

Short Synacthen Test

Abstract Background: Exogenous steroid use is the most common cause of central adrenal insufficiency. Depending on the duration and strength used, it may take months to years for the hypothalamic-pituitary-adrenal (HPA) axis to recover after the steroid is stopped. We report a case of iatrogenic hypoadrenalism with persistent suppression of the HPA axis for 13 years, discovered later to be due to a second pathology. Case: A 48 year old lady presented in 2005 with weight gain of 20 kg over 1 year and florid Cushingoid features. 9AM cortisol was undetectable (<12 nmol/L). History taking revealed use of oral dexamethasone at various dosages over the past 9 years for her knee pains. A diagnosis of iatrogenic adrenal insufficiency was made. She was started on hydrocortisone replacement, and was advised to stop the over-the-counter steroids. By 2011 her short Synacthen test (SST) showed much improved functioning of the HPA axis (cortisol 182 (0 min) -> 329 (30 min) -> 408 nmol/L (60 min) [N peak>500 nmol/L]), and she was back to her usual body weight. However, subsequent monitoring revealed declining trend of 9AM cortisol from 135 nmol/L (2013) -> 99 nmol/L (2014) -> 57 nmol/L (2015) -> 64 nmol/L (2016) -> 18 nmol/L (2017) [N 166–507 nmol/L]. Hydrocortisone compliance and abstinence from exogenous steroids was confirmed with the patient. The ongoing hypofunction of the HPA axis was continually attributed by multiple physicians to her history of prolonged use of dexamethasone. In 2018, at the age of 60, the lady presented with new onset headaches, blurred vision, and bitemporal hemianopia for 3 months. MRI showed a 1.8x1.8x3.5 cm (WxAPxH) pituitary mass with suprasellar extension compressing the optic chiasm. Blood tests revealed panhypopituitarism: SST cortisol 17 -> 59 -> 49 nmol/L, ACTH 2.7 pmol/L [N <10.1 pmol/L]; fT4 9.5 pmol/L [N 12–22 pmol/L], TSH 0.97 mIU/L [N 0.27–4.2 mIU/L]; LH <0.1 IU/L, FSH 0.52 IU/L (menopause at age of 48); IGF-1 27 µg/L [N 41–279 µg/L]; prolactin 17 mIU/L [N 102–496 mIU/L]. After partial excision of the mass her vision improved, but remained dependent on hydrocortisone and thyroxine supplements. The lesion was pathologically proven to be a pituitary macroadenoma. Discussion: This case presents the uncommon course of a patient who had almost recovered from iatrogenic hypoadrenalism, only to lapse back into worsened central adrenal insufficiency, as part of panhypopituitarism related to an undiagnosed pituitary mass. In retrospect, the unusually protracted state of hypocortisolemia and the atypical waxing and waning HPA axis should have alerted one to consider alternative etiologies at work. As LH-FSH and GH deficiencies commonly develop before ACTH and TSH deficiencies in most pituitary macroadenomas, a lower threshold for testing the other anterior pituitary hormones followed by imaging of the pituitary could have picked up the tumor earlier in this patient.

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EGFR T790M-Positive Lung Adenocarcinoma Metastases to the Pituitary Gland Causing Adrenal Insufficiency: A Case Report

Case Reports in Oncological Medicine ◽

10.1155/2018/2349021 ◽

2018 ◽

Vol 2018 ◽

pp. 1-4 ◽

Cited By ~ 1

Author(s):

Michael L. Adashek ◽

Kenneth Miller ◽

Arit A. Silpasuvan

Keyword(s):

Lung Adenocarcinoma ◽

Adrenal Insufficiency ◽

Growth Factor Receptor ◽

Secondary Adrenal Insufficiency ◽

Pituitary Mass ◽

Morning Cortisol ◽

Metastatic Lung ◽

History Of ◽

Epidermal Growth ◽

Egfr T790m

A 64-year-old man, with history of micropapillary thyroid cancer and epidermal growth factor receptor-positive lung adenocarcinoma with no evidence of active disease for 3 years after chemotherapy and radiation on erlotinib, presented with fatigue, nausea, lack of appetite, and xeroderma. A screening magnetic resonance image of the patient’s head demonstrated a new bilateral pituitary mass. Initial evaluation revealed low morning cortisol, and the patient was diagnosed with adrenal insufficiency. His symptoms rapidly improved with maintenance glucocorticoids. Soon thereafter, the patient developed an acute visual deficit secondary to enlargement of the pituitary mass, and biopsy revealed EGFR T790M positive metastatic lung adenocarcinoma. Hence, we present a rare case of metastatic lung adenocarcinoma to the pituitary causing secondary adrenal insufficiency.

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