SUN-055 Treading the Unknown Path: Tackling a Rare Form of Cushing Disease

Cushing's disease is caused by functional corticotroph adenomas of the pituitary, mostly noninvasive microadenomas. Classic Crooke's cells are nonneoplastic corticotrophs with cytoplasmic accumulation of cytokeratin filaments in response to glucocorticoid excess. Corticotroph adenomas exhibiting Crooke's change are rare and incompletely understood. We intend to define more clearly the clinicopathological features of Crooke's cell adenomas (CCA). Thirty-six CCAs were retrieved from the files of Mayo Clinic and from our (B.W.S., K.K.) consultation files. The number of informative cases varied for different criteria. Clinical follow-up was obtained in 31 cases. The 27 females and 9 males were 18 to 81 years of age (mean 46 years). At presentation, Cushing's disease was evident in 22/34 (65%); 81% were macroadenomas and 72% were invasive. All were initially treated by transsphenoidal resection. Twenty-five patients were followed for more than 1 year (mean 6.7 years). Of these, 15 (60%) developed recurrent tumor, and 6 (24%) had multiple recurrences. Lastly, 3 of these 25 patients (12%) died of tumor: 1 after multiple local recurrences and 2 from pituitary carcinoma. Compared with typical corticotroph adenomas, CCAs are aggressive. Most are functional adenomas occurring in middle-aged women and are invasive macroadenomas prone to recurrence. Morbidity and mortality rates are substantial. CCAs represent a distinct entity that should be separated from corticotroph adenomas without Crooke's hyaline change.

Co-existence of pituicytoma and corticotroph adenoma in a patient with Cushing's disease

Corticotroph adenomas rarely show Crooke's hyaline change in neoplastic cells, a feature similar to that of normal corticotroph cells exposed to excess cortisol. Crooke's cell adenomas are usually associated with Cushing's disease. Nonfunctioning examples are uncommon. We report two clinically silent corticotroph adenomas featuring extensive Crooke's hyalinization in neoplastic cells. The two patients were 49 and 59 yr of age and neither had Cushing's disease. Serum and urinary cortisol were normal. One patient had elevated serum adrenocorticotropic hormone. In our experience, the two patients accounted for 0.4% of pituitary adenomas operated on from January 1992 to December 2001 and 3.5% of all corticotroph adenomas. The two lesions had features of the subtype 1 silent corticotroph adenoma. Cytogenetic analysis performed on one lesion showed a normal karyotype (46;XY). Hyalinization in clinically silent Crooke's cell adenoma indicates that hyaline changes do not always relate to excess cortisol. It is known that neoplastic Crooke's cells show immunoreactivity for glucocorticoid receptors stronger than nontumorous Crooke's corticotrophs. This fact suggests that receptor overexpression or lack of receptor downregulation may result in hypersensitivity of neoplastic Crooke's cells to physiologic cortisol plasma levels.

While it has been shown that atrial natriuretic factor (ANF) is able to inhibit CRH-stimulated ACTH secretion in vitro, in normal men conflicting results on its effect on ACTH/cortisol responses to insulin and CRH have been reported. Since no data are available concerning the possible influence of ANF on the hypothalamic-pituitary-adrenal axis in states of ACTH hypersecretion, the effect of ANF on pituitary-adrenal function in basal conditions and after CRH stimulation has been investigated in patients with Cushing's (n = 4) and Addison's disease (n = 4). On two different days all patients underwent the following procedures: (a) alpha-human ANF was infused, after a priming dose of 100 ng i.v., at a rate of 0.01 microgram/kg/min over 5 hours. After 120 minutes of ANF infusion, oCRH (1 microgram/kg) was i.v. injected as a bolus; (b) vehicle infusion was given over 5 hours and at 120 minutes oCRH was injected. Plasma ANF, ACTH, cortisol, aldosterone, renin activity and K+ were measured; heart rate and blood pressure were monitored. In Cushing's disease plasma ANF rapidly increased within 30 minutes of the exogenous peptide infusion (from 27 +/- 5 to 73 +/- 14 pmol/l; mean +/- SE), whereas in the vehicle study its concentration was unchanged. During the first 2 hours of both tests no significant modifications in ACTH levels were observed. After CRH the plasma ACTH peak was unchanged. Serum cortisol levels progressively declined during the first 2 hours of ANF infusion (from 778 +/- 150 to 461 +/- 48 nmol/l; P < 0.05), whereas no changes were observed during vehicle. After CRH serum cortisol rose to similar peaks. Plasma aldosterone levels were significantly reduced during the first 2 hours of ANF infusion (from 81 +/- 20 to 35 +/- 7 pmol/l P < 0.05), whereas no changes were found during vehicle. A similar aldosterone rise was induced by CRH during either vehicle or ANF. Mean plasma renin activity slightly declined and the changes were similar on both occasions. In Addison's disease ANF levels rose within 30 minutes of the peptide infusion (from 12 +/- 1 to 49 +/- 8 pmol/l), while they were unchanged during vehicle. A slight decline in ACTH levels in the first 2 hours was observed during either vehicle or ANF infusion. After CRH the plasma ACTH peaks were similar. Mean plasma renin activity was unaffected by vehicle, while ANF caused a decline during the first 2 hours (from 13.4 +/- 0.8 to 7.7 +/- 0.3 ng/ml/h). In all patients, heart rate, blood pressure and K+ were only slightly affected on both occasions. (1) In patients with corticotrophin hypersecretion ANF does not influence basal and CRH-stimulated ACTH secretion; (2) in Cushing's disease ANF inhibits cortisol and aldosterone basal secretion; this effect is not mediated by ACTH and is over-ridden by CRH stimulation.

Disclosure: J. Hodge: None. S. Idriss: None. I. Jamal: None. R. Panta: None. Background: Crooke cell pituitary adenomas are corticotroph adenomas with Crooke’s cell changes, which are cytoplasmic accumulation of cytokeratin filaments in response to glucocorticoid excess. They are aggressive, invasive tumors, typically macroadenomas, with a high rate of Cushing’s disease and post -treatment (surgery and/or radiotherapy) recurrence. We present a case of Crooke cell pituitary adenoma without a Cushingoid appearance. Clinical Case: A 66-year-old Hispanic male with a 16-year history type II diabetes mellitus with retinopathy, presented with a pituitary macroadenoma at age 60. This was found incidentally when he had a brain CT for evaluation of vertigo. Subsequent brain MRI demonstrated a large 2.4 x 2.0 x 1.7 cm pituitary macroadenoma with extension into the suprasellar cistern and the left cavernous sinus. He was asymptomatic, without Cushingoid features. Hormonal evaluation revealed central hypogonadism and hypothyroidism, mildly elevated prolactin of 39.3 (4-15.2 ng/mL) and morning cortisol level of 12.7 (6-18.4 ug/dL). A 24-hour urine cortisol was normal. He was started on testosterone and thyroid hormone replacement therapy. His diabetes mellitus became progressively difficult to control with a peak HbA1C of 10.1%, about 7 years prior the macroadenoma finding. His HbA1C remained persistently elevated in the 8.1-9.5% range despite being on 6 anti-hyperglycemic agents, including basal insulin. A morning ACTH level 4 years after the initial visit, was 115 (6-50 pg/mL) with a cortisol level of 13.7 (6-18.4 ug/dL). Repeat morning ACTH and cortisol levels 7 months later were very similar. 5 years after the macroadenoma finding, he was noted to have worsening glaucoma, which was believed to be due to optic nerve compression. Therefore, he underwent endoscopic transphenoidal resection for tumor debulking. Pathology supported the diagnosis of Crooke cell corticotroph pituitary adenoma. Repeat brain MRI 3-months post-surgery demonstrated residual tumor, but normal optic chiasm and optic tracts. He had an abnormal dexamethasone suppression test prior to surgery (cortisol 6.4 ug/dL) and continued to do so post-operatively (cortisol 3.7 ug/dL with persistently elevated ACTH). Just prior to his surgery, testosterone replacement therapy was held. Total testosterone level after surgery was normal 309.6 (280-800 ng/dL) and free testosterone 7 (5-21 ng/dL); he remained off replacement therapy. Conclusion: Crooke cell pituitary adenomas are rare with limited data on prognosis and guidance for clinical management. Some patients may have subtle features of hypercortisolism, such as difficult to control diabetes mellitus, without an overt Cushingoid appearance. Presentation: 6/1/2024

Disclosure: M. Taleb: None. F. Manas: None. S. Levy-Basso: None.Background: Crooke Cell Adenoma (CCA) is an aggressive yet rare subtype of pituitary adenoma. The first case was reported in 1981, while the first description of the characteristic Crooke’s hyaline changes in corticotroph cells was made in 1935. Specifically, CCA is a variant of T-PIT-driving corticotroph adenomas characterized by the deposition of cytoplasmic, perinuclear cytokeratin (CK) filaments, leading to hyaline changes in the neoplastic cells. It can present as a functioning corticotroph adenoma, leading to Cushing’s disease, or rarely it can be clinically silent. Patients with CCA often have poorer endocrinologic outcomes compared to those with more typical corticotroph adenomas, with less frequent post-operative hormone normalization and a higher likelihood of persistent hypercortisolism. In addition to being clinically aggressive, there is a high rate of recurrence following surgical resection. Clinical Case: A 58-year-old female presented with a new onset headache, double vision, and dizziness. CT head incidentally noted an enlarged pituitary (up to 11mm), with mild suprasellar extension and contact with optic chiasm. MRI showed an acute infarct in the paramedian pons and cerebellar hemisphere and confirmed a cystic pituitary lesion, measuring 8 x 12 mm, projecting slightly into the suprasellar cistern and abutting the inferior surface of the optic chiasm without significant displacement. The hormonal evaluation was significant for an elevated ACTH at 70 pg/ml (normal: 7-63 pg/ml) and a non-suppressed dexamethasone suppression test. The rest of the studies including prolactin, thyroid studies, random cortisol, 24-hour urine cortisol, and IGF-1 were within normal limits. The patient underwent resection of the pituitary tumor four months later due to worsening vision changes. Histopathology showed a densely granulated corticotroph PitNET with focal Crooke cell change, with strongly positive synaptophysin and ACTH in the neoplastic cell population. Post-operatively, the patient experienced adrenal insufficiency requiring hydrocortisone replacement. The two-month follow-up MRI was stable with no residual enhancing tissue. Of note, the patient reports a similar history of pituitary adenoma and Cushing's disease in her first-degree cousin, who underwent surgery but had recurrence of the disease 6 years later. Conclusion: Given the higher likelihood of recurrence of CCA and poorer endocrinologic outcomes when compared to other typical pituitary corticotroph adenomas, close monitoring of hormonal levels and imaging at regular intervals is imperative. Unfortunately, due to the rarity of the condition, no specific guidelines are available. Although there is no clear genetic component to CCA, there is a potential hereditary factor if it occurs in the context of familial syndromes.Presentation: Monday, July 14, 2025

Crooke's cell adenoma (CCA), characterized by massive Crooke's hyaline change in corticotroph adenoma, causes a rare subtype of Cushing's disease. In contrast to ordinary corticotroph adenomas, CCAs are generally aggressive and present as invasive macroadenomas, which are refractory to both surgery and radiotherapy and have a high-recurrence rate. Moreover, some patients with CCA present with distant or craniospinal metastases. Currently, there are no effective standard therapies for CCA. We report a patient with Crooke's cell carcinoma who presented with local invasion and liver metastases, which was refractory to conventional therapeutic modalities including transsphenoidal surgery, radiosurgery, medications, and hepatic transcatheter arterial embolization. After all these treatments failed, the patient had monthly temozolomide administrations, resulting in gradual clinical improvement and biochemical data that were consistent with tumor shrinkage. In glioblastoma, low O(6)-methylguanine DNA methyltransferase (MGMT) expression is associated with epigenetic gene silencing and predicts a better response to temozolomide. We thus investigated MGMT expression, immunohistochemically, in seven CCAs (five invasive macroadenomas and two invasive microadenomas) and 17 ordinary-type adenomas (OTAs; three noninvasive macroadenomas, 12 noninvasive microadenomas, and two invasive microadenomas) from patients with Cushing's disease. In seven CCAs, all five invasive macroadenomas exhibited low MGMT expression, defined as <5% nuclear MGMT staining. In 17 OTAs, only one adenoma showed low MGMT expression. In Cushing's disease, invasive macroadenomas including CCA usually have low-MGMT expression. Temozolomide thus may be a new therapeutic option for invasive macroadenomas such as CCA particularly when conventional treatments are ineffective.

A minority of corticotroph adenomas are not related to Cushing's disease so that they have been defined “silent corticotropinomas“. Silent ACTH adenomas present with symptoms of mass effect, they are often haemorrhagic and show more aggressive behaviour than the conventional pituitary adenomas. Likely deriving for the POMC cells of the pars intermedia, silent corticotroph adenomas have been considered a separate entity within the spectrum of ACTH-producing adenohypophysial tumours. We studied 20 patients with non-functioning ACTH adenoma operated over the period January 1992– April 2003 at the Bellaria Hospital, Bologna, Italy. All had normal free urinary 24 hr cortisol level. Nine were female. Their age ranged from 34 to 77 years (mean, 52 years). Despite normal urinary cortisol, serum ACTH was markedly elevated in two patients (42 and 89.6 pmol/L, respectively; normal, 2–11) and slightly increased in 3. Radiologically, all lesions were macroadenoma and 12 were invasive. Cystic component was present in 5. Pathological examination revealed 8 adenomas type I, 3 of which were Crooke's cell adenomas, and 12 lesions of type II. One tumour was atypical in that it showed mitoses, MIB-1 labelling index higher that 3% and p53 nuclear over-expression. Pseudopapillary architecture due to poor cell-to-cell cohesion predominated in the majority of lesions. After a follow-up ranging from 12 to 136 months (mean, 54 months), three patients experience local recurrence but none died of disease. Silent corticotroph adenomas were compared with Cushing's related adenomas, particularly with the 13 macroadenomas operated in the same period. In these latter lesions, symptoms of mass effect were less common than in the silent tumours. Percentage of invasion was similar in the two groups whereas cystic change was more common in silent corticotropinomas. Persistence/recurrence rate was as high as noted in the silent adenoma groups. Pseudopapillary pattern was also a common finding on Cushing-related macroadenomas. Finally, we studied 5 silent corticotroph carcinomas. Patient's age ranged from 26 to 58 years. They had normal serum and free urinary cortisol as well as normal serum ACTH. All tumours were invasive macroadenoma. Histologically, 3 primary tumours were indistinguishable from conventional silent ACTH adenomas and 2 had features of atypical adenoma. All patients experienced local recurrence and, after a follow-up ranging form 2 to 23 years, all had metastases, 3 outside the central nervous system. Four patients died of disseminated disease and 1 of myocardial infarction. No patient developed Cushing's disease. Many of their clinicopathological features were similar to those of previously reported Cushing's disease related carcinomas. Our results suggested that some clinical and pathological features of silent corticotroph adenomas and carcinomas overlap with those of Cushing-related lesions. Therefore, silent adenomas are more likely part of the continuum of ACTH-producing tumours than a separate entity.

Although somatostatin inhibits a variety of pituitary and non-pituitary hormones, not univocal data on its effects on ACTH release have been reported so far. In this study we investigated the effects of somatostatin or octreotide on ACTH levels of patients with corticotropin hypersecretion: 7 patients with Addison's disease, 2 patients previously adrenalectomized for Cushing's disease, 4 patients with Cushing's disease and 3 patients with ectopic ACTH syndrome. Plasma ACTH and cortisol levels were determined after somatostatin (500 micrograms over 60 min) infusion or octreotide (100 micrograms sc) injection. In 5 other patients with Cushing's disease ACTH and cortisol responses to CRH (1 microgram/kg iv) were evaluated in basal conditions and after octreotide acute administration. In no patients with Addison's disease any inhibitory influence of somatostatin (delta % = -21, -25) or octreotide (delta % = -38 +/- 12 vs -39 +/- 12 after saline) on plasma ACTH was found. Somatostatin did not significantly inhibit plasma ACTH in the two patients previously adrenalectomized for Cushing's disease and in 3 patients with Cushing's syndrome; in other 4 patients with Cushing's syndrome octreotide did not affect plasma ACTH levels. In 5 patients with Cushing's disease the plasma ACTH and cortisol responses to CRH were similar both before (ACTH from 9.9 +/- 1.7 pmol/L to 19.4 +/- 6.1 pmol/L; cortisol from 496 +/- 43.9 nmol/L to 923 +/- 355 nmol/L) and after octreotide injection (ACTH from 8.8 +/- 2.4 pmol/L to 19.1 +/- 8.2 pmol/L; cortisol from 510 +/- 54.6 nmol/L to 735 +/- 220 nmol/L). In conclusion, the acute administration of somatostatin or octreotide is not able to modify ACTH levels in patients with corticotropin hypersecretion either due to hypocortisolemic state or consequent to ACTH-secreting pituitary or ectopic tumors; moreover, octreotide does not affect the pituitary-adrenal responsiveness to CRH in patients with Cushing's disease.

Crooke's corticotropinomas are the unique cause of Cushing's disease. The majority of them are aggressive macroadenomas, refractory to conventional therapy, with a high recurrence rate. The aim of the study was the presentation, in relation to data from the literature, of a case of a patient with ACTH-dependent Cushing's syndrome caused by recurrent Crooke's cells corticotropinoma, who achieved 33-month complete remission after treatment with temozolomide (TMZ). A 54-year-old man was diagnosed with Cushing's disease five years earlier on the basis of a typical clinical picture and hormonal tests. MRI revealed 32 × 29 × 24 mm macroadenoma. The patient underwent three subtotal selective transsphenoidal adenomectomies without retirement of hypercortisolaemia. A postoperative pathologic exploration revealed a densely granulated corticotroph Crooke's cells adenoma with MIB-1 index < 1%. Because of the large size of the tumour with its expansion to both cavernous sinuses and suprasellar region together with a compression of the optic chiasm, the patient was disqualified for gamma-knife. Due to an exhaustion of all conventional therapeutic options the patient was qualified to TMZ therapy. The standard dose of TMZ (150 g/m²) for five days every 28 days was implemented. After three courses of TMZ pronounced regression of tumour size with a marked hormonal and clinical improvement was certified. After six courses, consecutive tumour regression was observed. Nine courses resulted in a total radiological tumour shrinkage and hormonal normalisation. Despite the cassation of TMZ treatment the complete remission of the disease maintained for 33 months. Temozolomide can be an effective treatment option in invasive Crooke's cell corticotropinoma. (Endokrynol Pol 2016; 67 (5): 526-533).

Somatic mutations in the ubiquitin-specific peptidase USP8 gene were recently detected in one- to two-third(s) of corticotroph adenomas of Cushing's disease (CD). These mutations may lead to the deubiquitination of EGFR, thereby increasing EGFR signaling, which has been implicated in ACTH hypersecretion. Our objective was to determine the impact of USP8 mutations on the clinicopathological features of CD. USP8 mutations as well as clinicopathological characteristics were examined in 60 corticotroph adenomas including 15 Crooke's cell adenomas (CCAs), a rare histological variant presenting with generally aggressive behavior, using qRT-PCR and/or immunohistochemistry. USP8 mutations were exclusively detected in women, except for one case, with a prevalence of 42.2% in non-CCA and 13.3% in CCA (overall 35%). Clinically well-behaved presentations including microadenoma and curative resection were more common in mutated cases. The expression of EGFR was not associated with the mutation status. In contrast, mutated tumors expressed significantly higher levels of POMC, SSTR5, and MGMT. Microadenomas that strongly express POMC were common among mutated tumors, which may lead to the mechanisms by which very small adenomas secrete excess ACTH to present overt CD. While USP8 mutations were less likely to enhance tumorous ACTH hypersecretion via EGFR-mediated activation, the presence of USP8 mutations may predict favorable responses to the somatostatin analog pasireotide, which exhibits high affinity for SSTR5. In contrast, non-mutated aggressive tumors such as CCA may respond better to the alkylating agent temozolomide because of their significantly weak expression of MGMT.

To investigate prognostic indicators in an aggressive Crooke's cell adenoma of the pituitary. The surgically removed tumor was studied by histology, immunohistochemistry and transmission electron microscopy. An aggressive invasive sellar tumor removed by repeated surgeries from a 43-year-old woman with pituitary related Cushing's disease was classified as a Crooke's cell adenoma of the pituitary. The application of several cell proliferation markers confirmed the aggressive nature of the tumor. The investigation of the present case provides additional evidence that pituitary Crooke's cell adenomas may possess aggressive behavior.

The ACTH, cortisol and LH responses to low dose (0.8 mg/h) naloxone 90 min infusion were investigated in seven patients with untreated Cushing's disease, six patients with Addison's disease and four control subjects. Naloxone had no effects on ACTH hypersecretion or normal ACTH levels. These data confirm that naloxone cannot provide additional diagnostic or therapeutic approaches in ACTH hypersecretion syndromes, mainly in Cushing's disease. The mean percentage LH levels did not significantly change during low dose naloxone in controls or patients with Cushing's and Addison's diseases. This suggests that increased endogenous opioid peptides in these diseases may not modify the LH responses to low dose of naloxone. However, since three of five adults with Cushing's disease had increased LH levels during naloxone, further studies may be indicated.

Crooke's cell adenoma (CCA) is an aggressive subtype of corticotroph adenoma; however, CCA is associated with a high incidence of low expression of methyl guanine methyl transferase (MGMT), suggesting that temozolomide (TMZ) treatment might be effective for this tumor type. The case of a 56-year-old woman with Cushing's disease caused by a pituitary CCA is presented. At the age of 38 years, the patient presented to our hospital with polyuria and a visual field defect. MRI and laboratory studies showed a 4.5-cm-diameter pituitary tumor with plasma adrenocorticotropic hormone (ACTH) and serum cortisol levels of more than 500 pg/mL and 40 μg/dL, respectively. At 39 years of age, the patient underwent a craniotomy, and her plasma ACTH and cortisol levels decreased to less than 200 pg/mL and 10 μg/dL, respectively; however, these hormone levels increased gradually to 3,940 pg/mL and 70 μg/dL, respectively, by the time the patient was 56 years old. Histopathological re-examination of the previously resected specimen showed that the pituitary tumor was MGMT-negative CCA. TMZ treatment after the second operation decreased the plasma ACTH levels from 600-800 pg/mL to 70-300 pg/mL. No signs of recurrence were observed in the seven years following these treatments with added prophylactic radiation therapy. These clinical findings suggest that TMZ treatment to patients with CCA accompanied with elevated ACTH may be good indication to induce lowering ACTH levels and tumor shrinkage.

Disclosure: M.N. Abdou: None. H. Alhumaidi: None. Background: Current recommendations for steroids replacement in the immediate post-operative (post op) period after transsphenoidal surgery (TSS) for patients with Cushing’s Disease (CD) are heterogenous and can be misleading. Monitoring daily morning cortisol for 72 hours post TSS with replacing steroids only after detecting low morning cortisol or signs of adrenal insufficiency (AI) has been mentioned in several studies. While some studies recommend either empiric steroids replacement on discharge regardless of status of remission or longer hospital stay for closer cortisol monitoring, others recommended monitoring for 3-4 days and starting steroids on discharge only if morning cortisol was &amp;lt; 415 nmol/L. Case: 60 years old female with a history of type 2 diabetes mellitus, hypertension and dyslipidemia was referred for an evaluation of a pituitary macroadenoma. She had an incidental finding of a pituitary mass measuring 25 mm on a CT brain obtained after a fall 3 months prior to her current visit. MRI pituitary gland revealed a 25x23x22 mm suprasellar mass with cavernous sinus invasion. She reported weight gain and worsening of diabetes control over the 2 years prior to her presentation. On exam, weight was 80 kg, BMI 32.5, BP 110/69, vital signs were otherwise normal. She had central obesity, facial plethora, and frontal hair thinning. Hormonal workup showed elevated 1 mg dexamethasone suppression test: 341 nmol/L (&amp;lt;55). 24h UFC was also high 233 nmol/24 hours (38-208). Morning cortisol 15.5 mcg/dl (6-18) with ACTH 228 pg/ml (7.2-63.3). Prolactin 581 mIU/L (58-418). FSH and LH were at the premenopausal range. TSH, FT4, and IGF-1 were normal. HBA1C 8%. Results were consistent with CD with central hypogonadism and mild elevation of prolactin likely due to stalk effect. Patient was admitted to the hospital for TSS. She had no surgical complications, and no steroids were used to monitor remission. Daily morning cortisol was measured after the surgery, readings were (1631, 668, 469, 224, 318, 110 nmol/l) day 1-6 (D1-D6) post op. She was started on oral Hydrocortisone (HC) 15 mg in the morning and 10 mg in the afternoon on D6 post op after documentation of cortisol level of 110 nmol/l. She was vitally stable and had no signs of AI before starting steroids. 1 day after starting oral HC she developed hypotension and hyponatremia. IV HC 100 mg was given immediately followed by 50 mg every 6 hours. Blood pressure improved with stress dose steroids. She was discharged home on HC 20 mg three times daily, tapered to reach 15, 10 over a period of 2 weeks. Conclusion: We present a case of CD that had a nadir morning cortisol on D6 post op in whom a diagnosis of fatal AI would have been missed if recommendations from some studies were followed. This case highlights the importance of prolonged monitoring for adrenal insufficiency if steroids were not used after surgery for CD. Presentation: 6/1/2024