Low-dose Dexamethasone Suppression Research Articles

The 1-mg overnight low-dose dexamethasone suppression test cut-off in establishing the diagnosis of Cushing's syndrome

The 1-mg overnight low-dose dexamethasone suppression test cut-off in establishing the diagnosis of Cushing's syndrome

Retrospective Study on Trilostane Titration Dose Treatment in Dogs with Terminal Stage of Hyperadrenocorticism

Abstract Hyperadrenocorticism (HAC) in dogs is routinely treated with trilostane single-dose (CTG) which is reported to cause adverse reactions. The current retrospective study of several dogs with terminal stage of HAC aimed to compare the clinical, hematological, and biochemical effects of trilostane titration-dose treatment (TTG) with the single-dose treatment (CTG). All clinical cases (n=7) were confirmed on HAC by anamnestic, clinical, hematology, biochemistry, and low-dose dexamethasone suppression test findings, indicative for Cushing’s disease. Two cases were treated with CTG (2.2-6.7 mg/kg, single dose daily) and their treatment was discontinued on the second week due to adverse reactions. The TTG cases were treated for up to 12 weeks (0.5 mg/kg once daily for 7 days, and then with 0.5 mg/kg twice daily for 7 days). Blood samples and clinical checks were performed on 0., 4., and 12. weeks of the treatment. Hemoglobin was non-significantly higher in TTG at 12 weeks. Alanine transaminase was significantly lower in the TTG cases on the 12. week of the treatment (78.04±15.37 U/L) compared to the 0-week (137.81±24.03 U/L), and 4-week samples (131.92±23.36 U/L). No significant differences were observed with the CTG cases. Alkaline phosphatase was significantly lower on 12-week samples in TTG (251.02±93.06) compared to the 4-week (567.94±283.93 U/L), and 0-week samples (1,341.84 U/L). In conclusion, TTG has indicated to have significantly higher tendency to decrease alanine transaminase and alkaline phosphatase, alleviating the negative effects on the liver. The clinical findings were more adverse for the CTG.

The Overnight Low-Dose Dexamethasone Suppression Test Can Be Used to Evaluate Patients With Chronic Kidney Disease.

The Overnight Low-Dose Dexamethasone Suppression Test Can Be Used to Evaluate Patients With Chronic Kidney Disease.

P-47 Rare case of acromegaly due to plurihormonal pituitary adenoma and ACTH-independent Cushing syndrome

Abstract Introduction The concurrence of acromegaly and Cushing syndrome is infrequent. Pituitary adenomas are responsible for acromegaly and for Cushing syndrome in about 95% and 80% of cases respectively. Except adrenal adenoma, the other causes of Cushing syndrome remain rare. We here describe a case of a Tunisian patient with acromegaly due to plurihormonal pituitary adenoma and ACTH-independent Cushing syndrome with bilateral macronodules. Clinical Case A 35-year-old male patient was diagnosed with acromegaly by acrofacial dysmorphia. He had a family history of type 2 diabetes mellitus and hypertension but no endocrine diseases. He has diabetes mellitus for 15 years, hypertension and obstructive sleep apnea. Physical examination showed multiple blue nevi in the trunk. IGF-1 was elevated (1680ng/mL) and GH levels were not suppressed after an oral glucose load (nadir 78ng/mL). He had hypogonadotropic hypogonadism with normal prolactin (9,66ng/mL). Basal cortisol, FT4 and TSH levels were in the normal ranges. Pituitary MRI showed pituitary macroadenoma of 25×20.7 mm, invading both cavernous sinuses and compression of optic chiasma. He underwent transsphenoidal resection with histology confirming a prolactin, GH and LH co-secretory pituitary adenoma. He received postoperatively somatostatin analogue and cabergoline, in addition to external radiotherapy. Ultrasonography found infracentimetric EU-TIRADS 2 left nodule and multiple colloid cysts of the thyroid, testicles microlithiasis and no cardiac myxomas. Nine years after the diagnosis of acromegaly, bilateral adrenal adenomas (left:14 mm, right: 9 mm) were incidentally discovered by CT-scan done for abdominal pain. Low dose dexamethasone suppression test was carried out showing no suppression of cortisol and the low ACTH level confirmed ACTH-independent Cushing syndrome. Conclusion In our patient, at least two endocrine syndromes deserve to be mentioned. The first syndrome is Multiple Endocrine Neoplasia Type 1 but calcium and PTH levels were normal and there was no sign for neuroendocrine tumors. The second one is Carney's complex since our patient has acromegaly and multiple blue nevi which are two major criteria confirming the diagnosis. Cushing syndrome in Carney's complex is related to primary pigmented nodular adrenal disease characterized by micronodular hyperplasia. However, bilateral macronodules could be found in up to 30% of cases.

Subcentimeter Corticotroph Adenoma: an Evaluation of Diagnostic Elements

Cushing’s disease (CD) is an uncommon yet serious disorder, linked to increased morbidity and mortality. Diagnosis of these patients are complex, and emphasis should be placed on early detection for better management of these patients. The objective of this case report is to evaluate the diagnostic elements in the identification of a subcentimeter adrenocorticotrophic hormone (ACTH)-dependent pituitary adenoma. We report a case of a 26-year-old man who presented with extensive superficial fungal infection of the skin, unintentional weight gain, hypertension, dyslipidaemia as well as cushingoid appearance suspicious of hypercortisolism. Raised midnight plasma cortisol and 24-hour urinary cortisol levels warranted further investigation. Overnight and 48-hour low-dose dexamethasone suppression test (LDDST) were non-suppressed. Subsequent bilateral inferior petrosal sinus sampling (BIPSS) was not only efficient in differentiating pituitary from ectopic Cushing’s syndrome (CS) but was shown to be superior to magnetic resonance imaging (MRI) in lateralisation of the pituitary adenoma.

THU213 Posterior Reversible Encephalopathy Syndrome As A Rare Presentation Of ACTH-dependent Cushing Syndrome In A Pediatric Patient

Abstract Disclosure: E.E. Bell-Sambataro: None. C. Tatsi: None. P. Chittiboina: None. S.A. Bowden: None. Background: Cushing disease (CD), caused by ACTH-secreting pituitary adenoma, is the most common cause of Cushing Syndrome (CS) in children > 5 years of age. Hypertension is reported in up to 50% of pediatric cases with CS. We report a challenging pediatric case with a rare presentation of hypertensive emergency associated with CD. Clinical Case: A 6-year-old female with 3 month-history of rapid weight gain (8 kg), round face, and hypertrichosis presented to emergency department for abdominal pain from nephrolithiasis and was noted to have severe hypertension. While in ED, she developed status epilepticus and altered mental status. Brain MRI findings were consistent with posterior reversible encephalopathy syndrome (PRES). Her hypertensive encephalopathy gradually improved with aggressive anti-hypertensive and anti-epileptic therapy. Further studies confirmed hypercortisolism with markedly elevated urine free cortisol of 1288 ug/day (<18 ug/day) and lack of diurnal variation of serum cortisol (8 AM cortisol of 47.9 ug/dL, midnight cortisol of 20.3 ug/dL). ACTH level of 23 pg/mL suggested ACTH-dependent CS. Low dose (1 mg) dexamethasone suppression test (DST) failed to suppress 8 am cortisol (31.4 ug/dL). High dose DST (120 mcg/kg) suppressed serum cortisol to 67%- borderline threshold for CD, likely due to increased dexamethasone clearance by anticonvulsant. Pituitary MRI did not reveal a visible lesion. Desmopressin stimulation test showed stimulation of ACTH by 700% and cortisol by 160% suggesting pituitary source. Inferior petrosal sinus sampling showed a mildly increased gradient in central to peripheral plasma ACTH of 1.7 at baseline (>2) and post-stimulation of 2.5 (>3). ACTH gradient did not reach cutoffs for pituitary source, likely due to insufficient catheterization of petrosal sinus from anatomically small blood vessels. Given her severity, she underwent surgical pituitary exploration. Postoperative morning cortisol was <5 mcg/dL, with decreased midnight salivary cortisol level obtained 2 months after surgery. She developed post-operative central hypothyroidism but did not have diabetes insipidus. She had a 4 kg weight loss with increased height percentile 5 months after surgery and remains under close monitoring. Conclusion: PRES is a clinical-radiographic disorder characterized by seizures, encephalopathy with neuroimaging findings of reversible cortical and subcortical vasogenic edema. Hypertension induced by marked hypercortisolism precipitated by pain is likely the etiologic factor. Prompt recognition and treatment of PRES are crucial to prevent further life-threatening complications and permanent neurological damage. Early diagnosis and treatment of CD are critical to prevent associated morbidities. Pituitary exploration by expert neurosurgery team should be considered in patients with MRI-negative CD. Presentation: Thursday, June 15, 2023

THU647 Patient With Successful Conception During Treatment For Cushing Disease: Case Report

Abstract Disclosure: C. Iweha: None. E.K. Babler: None. M. Castillo: None. Introduction Cushing Disease (CD) is an endocrine disorder that predominantly affects women of childbearing age and is characterized by excess secretion of adrenocorticotropic hormone (ACTH) with hypercortisolism. We report a case of a woman with ACTH-dependent hypercortisolism treated with pasireotide who had a successful pregnancy while on treatment. Clinical Case A 27-year-old woman presented to the initial consult on 9/01/2011 with a 4-year history of ongoing symptoms of hirsutism, diaphoresis, oligomenorrhea, myalgia, and acne. A physical exam revealed an overweight female with mild facial acne and hirsutism. Family history included autoimmune disease in mother (lupus and multiple sclerosis). She was frustrated by the lack of a definitive diagnosis over 4 years; she was anxious and using multiple medications, including anxiolytics and analgesics, without relief of symptoms. Patient did not use alcohol and never smoked. Labs revealed initial morning (AM) cortisol = 26.9 µg/dL (normal range: 5-23 µg/dL) and ACTH = 14 pg/mL (normal: 6-58 pg/mL); 24-hour urinary cortisol was 110.6 µg/24 h (normal:<100 µg/dL) and serum ACTH =8 pg/mL. Low-dose (1 mg) dexamethasone suppression test reduced AM cortisol to 1.7 µg/dL and ACTH of 8 pg/mL. No evidence of adrenal adenoma on abdominal CT or pituitary adenoma on brain MRI, and IPSS confirmed diagnosis. Based on hypercortisolism and normal ACTH level, diagnosis was ACTH-dependent CD. We advised the patient to join a clinical trial for pasireotide, and she began treatment on 1/3/2013. She presented for follow-up on 6/17/2014 and reported improvement of some symptoms on 0.6 mg pasireotide twice daily, the highest dose she could tolerate. She reported experiencing chronic pain; medications included prescription analgesics, muscle relaxants, and anxiolytics. On 6/23/2015, our patient returned for a follow-up when she was 5.5 months pregnant. While on pasireotide, she became pregnant and subsequently left the study and discontinued treatment. She reported recurrence of hirsutism, acne, fatigue, and hyperemesis with discontinuation of pasireotide. Patient returned twice more during pregnancy and had a successful delivery and healthy infant. Clinical Conclusions Successful conception and pregnancy are unusual with CD due to fertility-inhibiting hormonal effects of excess cortisol. Some medications for CD impede pregnancy through their mechanism (eg, mifepristone). Our patient conceiving while on treatment is promising for women with CD. Although her CD symptoms returned when pasireotide was discontinued, she delivered a healthy infant; limited pasireotide data in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage. Our case underscores the potential for successful conception for women with CD when cortisol levels are normalized with treatment that avoids suppressing menstruation. Presentation: Thursday, June 15, 2023

SAT327 A Curious Case of Immune Checkpoint Inhibitor Induced Hypophysitis with Transient ACTH-dependent Hypercortisolism

Abstract Disclosure: M. Shi: None. F. AlRubaish: None. N. Gupta: None. V. Larouche: None. S. Christopoulos: None. The use of immune checkpoint inhibitors (ICI) has increased exponentially over the last decade as these agents have shown to substantially improve the prognosis in multiple advanced malignancies. Despite these important clinical benefits, ICI are associated with many immune-related adverse events (irAE). Endocrinopathies are the most frequent irAE and include autoimmune thyroid disorders, hypophysitis and primary adrenal insufficiency. These endocrinopathies often require long-term surveillance and hormone supplementation. We report a relatively novel irAE case of transient central hypercortisolism that progressed to hypopituitarism. A 72-year-old woman with metastatic melanoma on combined ICI therapy of nivolumab-ipilimumab developed subclinical hyperthyroidism (TSH <0.02 mU/L [reference range (RR) 0.40-4.50 mU/L]; FT4 20.2 pmol/L [RR 9.0-26.0 pmol/L]) eight weeks following initiation of her immunotherapy. At week 11, she was found to have refractory hypokalemia (initial potassium at presentation 2.3 mmol/L RR 3.5-5.5 mmol/L) and metabolic alkalosis (pH 7.57 [RR 7.35-7.45]; bicarbonate 39 mmol/L [RR 22-31 mmol/L]). Physical exam was unremarkable for Cushingoid features. Subsequent investigations revealed central hypothyroidism (TSH 0.02 mU/L [RR 0.40-4.50 mU/L]; FT4 8.1 pmol/L [RR 9.0-26.0 pmol/L]) and levothyroxine replacement was started. She also had evidence of hypogonadotropic hypogonadism (FSH 4.2 U/L [postmenopausal RR 25.8-143.9 U/L]; LH 1.5 U/L [postmenopausal RR 13.2-45.7U/L]) and central hypercortisolism with a morning cortisol of 1082 nmol/L [RR 172-497 nmol/L] and an ACTH level of 18.3 pmol/L [RR 1.6-13.9 pmol/L]. The low dose dexamethasone suppression test was not suppressed (morning cortisol at 983 nmol/L). She underwent imaging studies of her abdomen and brain which revealed normal adrenal and pituitary glands, respectively. Close pituitary function monitoring during endocrinology follow-up revealed persistent elevation of cortisol and ACTH levels until week 15, then a subsequent decline in both cortisol and ACTH levels for which she started hydrocortisone replacement. Further follow-up blood work revealed morning cortisol levels below 50 nmol/L [RR 172-497 nmol/L] with undetectable ACTH levels from week 16 onwards. The hydrocortisone and levothyroxine replacement were continued, and the patient remained asymptomatic throughout her follow-ups. This case highlights that a transient episode of ACTH dependent hypercortisolism may be an early marker prior to the development of central adrenal insufficiency from ICI-related destructive immune hypophysitis. Furthermore, our report highlights that physicians and other healthcare professionals should remain vigilant in monitoring laboratory progression in these patients, as early recognition facilitated timely management in our patient and prevented complications. Presentation: Saturday, June 17, 2023

THU015 Unilateral Adrenal Hyperplasia Causing ACTH-independent Hypercortisolism

Abstract Disclosure: N. Mogar: None. M.A. McConnell : None. R. Yu: None. J.E. Weinreb: None. Background: Adrenal cortical hyperplasia is defined radiographically as a non-malignant growth or enlargement of the adrenal glands. Adrenal hyperplasia is most commonly bilateral, with unilateral adrenal hyperplasia occurring less frequently. Unilateral adrenal hyperplasia has been associated with primary hyperaldosteronism, and there are only a few case reports describing unilateral adrenal hyperplasia associated with ACTH-independent hypercortisolism. Clinical Case: A 56-year-old man with sleep apnea was incidentally found to have a 4.6 cm left adrenal nodule found on computed tomography (CT) chest imaging. Adrenal CT revealed a heterogeneous 4.6 x 3.3 x3.7 cm left adrenal mass with internal calcifications and a portion of the mass measuring 38 Houndsfield units (HU). His 8AM serum cortisol level was 19.80 mcg/dL (5-23 mcg/dL). No ACTH level was collected; however, a serum DHEA-S level was 55 mcg/dL (32-240 mcg/dL). After low dose dexamethasone suppression test (LDDS), the serum cortisol level was elevated at 2.3 mcg/dL (<1.8 mcg/dL). Repeat LDDS revealed a cortisol level of 2.9 mcg/dL. A 24-hour urine free cortisol level was 27.2 mcg/24h (4-50 mcg/24h). Testing for pheochromocytoma and hyperaldosteronism was negative. The patient had no historical or physical signs of Cushing’s syndrome and no signs of malignancy. Due to concerning features on adrenal CT imaging (tumor size >4 cm, internal calcifications, and HU >10), the patient underwent unilateral adrenalectomy. The patient did not receive intraoperative corticosteroids and remained normotensive post-operatively. However, his post-operative 8AM cortisol level was <0.2 mcg/dL (5-23 mcg/dL) on two separate occasions. He was discharged on a short course of hydrocortisone, with eventual recovery of his hypothalamic-pituitary-adrenal (HPA) axis. Pathology revealed a diagnosis of cortical adrenal hyperplasia. Conclusion: The presence of postoperative hypocortisolemia demonstrates that this patient had ACTH-independent hypercortisolism. This case report would be one of few describing the rare diagnosis of unilateral adrenal hyperplasia associated with ACTH-independent hypercortisolism and would add to the sparse literature currently available on this condition. Additionally, this case report highlights the clinical significance of mild autonomous cortisol secretion (MACS); despite only having an unsuppressed cortisol level following LDDS, this patient was found to have a suppressed HPA axis after unilateral adrenalectomy requiring corticosteroids. Early identification and treatment of MACS and treatment of adrenal insufficiency following adrenalectomy is essential to prevent adverse events. Presentation: Thursday, June 15, 2023

FRI189 Alcohol-induced Non-neoplastic Hypercortisolism: Report Of Eight Cases And Review Of The Literature

Abstract Disclosure: A. Surani: None. T.B. Carroll: Consulting Fee; Self; Corcept Therapeutics. Research Investigator; Self; Corcept Therapeutics, Recordati. B.R. Javorsky: Consulting Fee; Self; Clarus. Research Investigator; Self; Recordati, Amryt Pharma. H. Raff: Consulting Fee; Self; Cerium Pharmaceuticals, Corcept Therapeutics. Research Investigator; Self; Cerium Pharmaceuticals. J.W. Findling: Consulting Fee; Self; Corcept Therapeutics, Recordati. Research Investigator; Self; Recordati. Alcohol intake stimulates the hypothalamic-pituitary-adrenal (HPA) axis. Alcohol-induced hypercortisolism (AIH) is an underrecognized clinical phenomenon thought to be of hypothalamic etiology. Patients with alcohol use disorder may masquerade as neoplastic hypercortisolism [Cushing syndrome (CS)] thus obscuring its diagnosis. We addressed this issue using newer, more accurate biochemical testing for the diagnosis of CS. We evaluated eight patients with AIH referred for possible CS (six for inferior petrosal sinus sampling, one with persistent CS after removal of an adrenal adenoma, and one for pituitary surgery). All patients had clinical features of hypercortisolism and plasma ACTH levels within or above the reference interval (RI) confirming a centrally mediated mechanism. All eight patients had abnormal low-dose dexamethasone suppression test (DST) [post DST serum cortisol 2.2-19.1 mcg/dL (RI<1.8)] and increased late-night salivary cortisol [8.2-71.0 nmol/L (RI<3.2)]. Only one patient had increased urine cortisol excretion. In contrast to patients with pituitary CS, the 5 patients tested had blunted or absent ACTH and cortisol responses to dDAVP. Two patients had adrenal nodules and one patient had abnormal pituitary imaging. Most patients initially underreported their alcohol consumption and one patient denied alcohol use. A marked elevation of blood phosphatidylethanol (PEth) was required in one patient to confirm excessive alcohol use. All the patients had significant elevations of liver function tests (LFTs) with AST>ALT. Review of the literature discovered 37 reported cases of AIH. These cases also had clinical and many biochemical findings that were similar to neoplastic hypercortisolism. Conclusion: AIH is an under-appreciated potentially reversible cause of non-neoplastic hypercortisolism that may be indistinguishable from neoplastic ACTH-dependent CS. Incidental pituitary and adrenal imaging abnormalities as well as under-reporting of alcohol consumption may further confound the diagnosis. Elevations of LFTs (AST>ALT) and subnormal ACTH and cortisol responses to dDAVP may be helpful in distinguishing AIH from neoplastic hypercortisolism. Measurement of PEth helps to confirm an alcohol use disorder. Presentation: Friday, June 16, 2023

FRI177 Cosyntropin Stimulation Testing Is More Selective Than Postoperative Day 1 Basal Cortisol for Diagnosing Secondary Adrenal Insufficiency Following Unilateral Adrenalectomy

Abstract Disclosure: S.H. Johnson: None. C. Zhang: None. P.T. Hangge: None. T.W. Yen: None. T. Shaik: None. K. Doffek: None. J.W. Findling: None. T.B. Carroll: None. D.B. Evans: None. S. Dream: None. T.S. Wang: None. Background: Secondary adrenal insufficiency (SAI) may occur in patients after unilateral adrenalectomy for adrenal-dependent hypercortisolism (HC) and/or primary aldosteronism (PA). Perioperative protocols include routine glucocorticoid replacement (GR) or selective GR based on postoperative day 1 (POD1) basal cortisol levels or cosyntropin stimulation testing (CST). This study aimed to assess if a POD1 basal cortisol level alone was predictive of an abnormal CST and the need for GR in patients following unilateral adrenalectomy for HC and/or PA. Methods: This is a single institution retrospective review of consecutive unilateral adrenalectomies performed for HC and/or PA from 9/2014-10/2022. Patients were grouped as overt hypercortisolism (OH;n=42), mild autonomous cortisol excretion (MACE;n=70), mixed PA/HC (n=22) or PA (n=73); 22 patients with PA did not have preoperative evaluation for HC. Preoperative morning cortisol after low-dose dexamethasone suppression testing (DST), was used to define MACE (1.8-4.9 µg/dL) and OH (≥5.0). POD1 CST was performed for all patients with HC and prior to 2021, all patients with PA. SAI was defined as basal cortisol ≤5 or stimulated ≤14 (≤18 before 4/2017). Receiver operating characteristic (ROC) curves and sensitivity analyses were performed to assess the sensitivity (SN) and specificity (SP) of cutoffs within the range of observed basal cortisol levels in predicting an abnormal CST and need for GR. Results: Of 207 patients, 152 had POD1 CST (93% OH, 96% MACE, 73% PA/HC, 41% PA). Of these, 80 (53%) had SAI (67% OH, 55% MACE, 44% PA/HC, and 33% PA). Of the 10 patients with PA and SAI, 5 did not have preoperative testing for HC. Overall, 81 patients were discharged on GR. Median (interquartile range [IQR]) duration of GR was 246 (127,557), 55 (38,207), 74 (16,185), and 26 (15,36) days in patients with OH, MACE, PA/HC, and PA, respectively. At a median follow-up of 142 days (IQR 42,617), 12 patients (5 OH, 6 MACE, 1 PA/HC) remained on GR. The SN/SP of a basal cortisol ≤10 in predicting GR was 92%/77% in patients with OH and 94%/73% of patients with MACE. Compared to initiation of GR based on basal cortisol ≤10, CST identified 4 patients with SAI in the combined OH and MACE cohorts who would not have received GR, and 11 in the combined cohort who did not require GR. For patients with PA and PA/HC, a basal cortisol ≤10 had SN of 100% and SP of 85% and 67%, respectively. The optimal basal cortisol for predicting SAI in patients with PA/HC was ≤5 (SN,SP 100%). Area under the curve for all ROC curves was >0.9. Conclusion: These results demonstrate that in patients who underwent unilateral adrenalectomy for HC, PA, or mixed PA/HC, POD1 CST improved identification of patients at risk for SAI compared to basal cortisol levels alone. While basal cortisol levels alone may be considered in patients with PA or mixed HC/PA, all other patients with HC should have POD1 CST to determine need for postoperative GR. Presentation: Friday, June 16, 2023

THU517 Aggressive Cushing’s: A Rare Case Of Pancreatic ACTHoma In A Young Female

Abstract Disclosure: O.C. Reyes: None. A. Sison: None. M. Villa: None. D. Dimayuga: None. Introduction: Adrenocorticotropic hormone-producing pancreatic neuroendocrine neoplasm (ACTHoma) is a rare type of pancreatic neuroendocrine tumor that causes ectopic adrenocorticotropic hormone syndrome. Cushingoid manifestations and metabolic abnormalities can occur rapidly. High index of suspicion is required for early diagnosis. Case: A 31-year-old Filipino female presented with facial and ankle swelling that occurred 6 weeks before the visit. She also had acne, easy bruising, amenorrhea and frequent mood swings. There was reported weight gain of 3 kg a month prior. She had no history of hypertension and diabetes, and had no unusual family history. At the time of admission, vital signs were blood pressure of 130/80mmHg, pulse of 92/min, respiratory rate 20/min and body temperature of 37.2C. Her body mass index was 28kg/m2. She had muscle atrophy of the upper and lower extremities, facial flushing, posterior cervical fat pad, abdominal violaceous striae, and skin pigmentation. Her external genitalia was normal, Tanner Stage 5 consistent with adult pattern. Neurologic exam was unremarkable. She was examined for Cushing’s syndrome. On initial tests, glucose was 406 mg/dl, HbA1C 10.7%, thyroid stimulating hormone 0.122 (NV: 0.55-4.78), Free T3 0.77 (NV: 2.3-4.2), Free T4 0.58 (NV: 0.89-1.76). Creatinine was 0.86 mg/dL, sodium was 140 mEq/L, potassium was 2.1 mEq/L showing hypokalemia. There was leukocytosis on her blood count, white blood cells 15,310/mm3 (neutrophils 94%, lymphocytes 3%). In the low-dose dexamethasone suppression test (DST), the serum cortisol concentration was 991.03nmol/L. Her adrenocorticotrophic hormone (ACTH) level was elevated at 577pg/mL. After high-dose DST, the serum cortisol concentration was > 1750 nmol/L. No tumor was observed on pituitary magnetic resonance imaging. On abdominal computed tomography (CT), a large, lobulated, heterogeneously-enhancing mass arising from the pancreatic body and tail measuring 7.5cm x 10cm x 10.9cm was seen. The mass had infiltrated the gastric fundus, and encased the splenic artery. Multiple non-calcified subcentimeter pulmonary nodules were observed on chest CT. CT-guided biopsy of the pancreatic mass was done. On microscopic examination, numerous atypical cells arranged with small clusters and sheets and scattered singly were found in the tumor. The cells had small to enlarged, hyperchromatic, ovoid to round nuclei and scant to ample delicate cytoplasm. On immunohistochemical staining, the tumor cells were stained positive for synaptophysin and chromogranin A, which are both neuroendocrine markers, as well as ACTH. However, the patient died prior to any definitive management. Conclusion: ACTHoma is a very rare disease that causes hypercortisolemia. Reporting of similar cases will provide insight into its clinical features, immunohistochemical characteristics, diagnosis, therapy, and prognosis. Presentation: Thursday, June 15, 2023

Total testosterone cut-off value indicating androgen-secreting tumor in premenopausal women with hirsutism.

There is insufficient data on which cut-off value must be used to measure the increase in total testosterone (TT) compared to the upper limit of normal (CULN) in the diagnosis of androgen-secreting tumor (ASTM) in female individuals with premenopausal hirsutism (FIPH). A total of 413 FIPH over 18 years of age who were admitted to the endocrinology clinic between May 2013 and 30 April 2018 were eligible for the study. Hormone profiles of the participants in the follicular phase and other information were obtained from their files. The androgen suppression ratio (ASR) was analyzed after 48 hours of low-dose dexamethasone suppression test (LDDST) in those whose TT CULN (nmol/L) increased two-fold. Idiopathic hirsutism was found in 193 participants (46.73%) and polycystic ovary syndrome (PCOS) in 200 (48.43%) and other sources of hirsutism; non-classical congenital adrenal hyperplasia (NCCAH) in 10 patients (2.42%), hyperprolactinemia in 6 patients (1.45%), ASTM of ovarian origin in 2 patients (0.48%), Cushing's disease in 1 patient (0.24%), and adrenal ASTM in 1 patient (0.24%). A cut-off value of two-fold CULN increase for TT sensitivity of 100% and a specificity of 99.5% in indicating an ASTM source, and ASR above 49% in LDDST sensitivity of 80% and a specificity of 100% in excluding an ASTM source, was used. At the TT level, a two-fold increase CULN in FIPH indicates an ASTM source. In addition, ASR after LDDST is a useful parameter in the exclusion of ASTM sources in the same patient population.

Factitious cushing's syndrome with unusual presentation: a case report and literature review.

A 40-year-old female patient who worked as a registered nurse presented with clinical features of CS but denied any exogenous corticosteroid use. The endocrine workup revealed that the patient had a high 24h urinary-free cortisol collection before admission. Subsequent evaluations showed low levels of morning cortisol and plasma adrenocorticotropic hormone along with a suppressed overnight low-dose dexamethasone suppression test, leading to an investigation of hypercortisolism. Unexpectedly, subsequent testing showed a normal 24h urinary-free cortisol level. Additionally, the patient was diagnosed with panhypopituitarism, the radiological investigations showed normal pituitary and adrenal glands. Despite consistently denying the use of corticosteroids, it was finally discovered that the patient had been surreptitiously taking prednisone and receiving multiple dexamethasone injections over the past few months. The patient received treatment through a gradual prednisone tapering regimen, accompanied by comprehensive psychiatric evaluation and management. This case underscores the exceptional rarity of factitious CS and emphasizes the importance of considering it as a potential differential diagnosis in hypercortisolism cases, particularly when the patient's medical history contradicts investigative findings. Furthermore, it highlights the criticality of adopting a multidisciplinary approach to investigate patients whose clinical presentation aligns with factitious CS.

Part II: Interactive case: Drug‐induced endocrine disorders

Part <scp>II</scp>: Interactive case: <scp>Drug‐induced</scp> endocrine disorders

Diagnostic cut-off values for the urinary corticoid:creatinine ratio for the diagnosis of canine Cushing's syndrome using an automated chemiluminescent assay.

Cushing's syndrome is one of the most common endocrinopathies in dogs. The preferred screening test for spontaneous Cushing's syndrome is the low-dose dexamethasone suppression test (LDDST). The diagnostic value of urinary cortisol:creatinine ratios (UCCR) is questionable. The aim of this study was to determine diagnostic cut-off values for UCCR testing in comparison with LDDST as a clinical reference standard and to calculate the sensitivity and specificity. Data from 2018 to 2020 were obtained retrospectively from a commercial laboratory. Both LDDST and UCCR were measured by automated chemiluminescent immunoassay (CLIA). The maximum interval between both tests was 14 days. The optimal cut-off value for UCCR testing was calculated by the Youden index. The sensitivity and specificity of these cut-off values for the UCCR test and LDDST were assessed by Bayesian latent class models (BLCMs). This study included 324 dogs with both UCCR test and LDDST results. The optimal UCCR cut-off value, calculated by the Youden index, was 47.4 × 10-6 . Any UCCR <40 × 10-6 was interpreted as a negative result, 40-60 × 10-6 as values in a gray zone, and >60 × 10-6 as positive. Using the cut-off of 60 × 10-6 , BLCM showed 91% (LDDST) and 86% (UCCR test) sensitivity and a specificity of 54% (LDDST) and 63% (UCCR test). Considering an 86% sensitivity and a 63% specificity, UCCR testing may be considered a first-line investigation to rule out Cushing's syndrome using CLIA analysis. Urine samples can be collected noninvasively at home by the owner, reducing the potential impact of stress.

Determination of dexamethasone level by liquid chromatography with tandem mass spectrometry after low-dose dexamethasone suppression test

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Abstract #1407012: ACTH Producing Pituitary Adenoma Found After Transsphenoidal Resection of Meningioma

ACTH-dependent Cushing's disease (CD) is a condition characterized by pituitary hypersecretion of ACTH, leading to adrenal cortisol upregulation. Hypercortisolism has long-term complications, notably metabolic syndrome, cardiovascular disease, and osteoporosis, to name a few. The incidence of CD is approximately 1-2 cases per million. ACTH can be secreted by pituitary macroadenomas and microadenomas, and in some cases, ectopic sources. This case report describes a case of ACTH-dependent CD caused by a pituitary microadenoma with a history of planum sphenoidal meningioma. 48-year-old female with a past medical history of planum sphenoidal meningioma s/p transsphenoidal partial resection, central hypothyroidism on levothyroxine, and hypogonadotropic hypogonadism presented with worsening truncal obesity and prediabetes. The physical exam was remarkable for obesity and hyperpigmentation of knuckles. Labs were significant for elevated AM cortisol at 27.2 mcg/dL with a significantly elevated ACTH level of 81.8 pg/L. Saliva cortisol at 11pm was also mildly elevated at 0.154 ug/dL. The cortisol level was not suppressed with the low-dose dexamethasone suppression test at 8.5 mcg/dL, while High-dose dexamethasone suppressed cortisol to 2.0 mcg/dL, indicating a possible pituitary source. Other biochemical tests such as Prolactin, TSH, and HGH levels were normal. MRI of the pituitary was performed to locate the potential source and was significant for hypo-enhancing lesions suspicious for bilateral synchronous pituitary microadenomas (9x5 mm right and 4x4 mm left). To confirm that there are no ectopic sources for the ACTH, a PET Dotatate scan was done and showed hypermetabolic meningioma corresponding to the findings of the pituitary MRI and confirmed no other abnormal focal radiotracer uptake. Non-functioning pituitary tumors are common, hence, to confirm the pituitary source of ACTH prior to surgery, she underwent inferior petrosal sinus sampling (IPSS). This revealed a significantly elevated ACTH secretion from the right microadenoma. Transsphenoidal resection of the pituitary tumor was performed. Post-procedure, AM cortisol levels were undetectable and ACTH level was low at 5.8 pg/mL. She was then started on hydrocortisone for presumed adrenal insufficiency post pituitary lesion resection. No signs of diabetes insipidus were shown after surgery—the patient will follow up with endocrinology for eventual weaning off hydrocortisone. Simultaneous occurrence of pituitary adenoma and meningioma without a history of radiotherapy is extremely rare, with only 49 cases described before 2019. Even more rare, is an ACTH secreting pituitary adenoma coexisting with a meningioma. IPSS procedure was performed after MRI in this case to get even more accurate localization of the source before surgical excision, as it is the best test to differentiate pituitary from ectopic ACTH-dependent Cushing’s. In approximately 1 out of 3 patients, remission is not achieved with surgical excision alone. For this reason, patients need post-operative monitoring and secondary medications to control their symptoms.

Psychosocial health modifies associations between HPA-axis function and brain structure in older age

BackgroundDysregulation of the negative feedback loop of the hypothalamic-pituitary-adrenal (HPA) axis may have damaging effects on the brain, potentially under influence of psychosocial health factors. We studied associations between functioning of the negative feedback loop of HPA-axis, measured with a very low-dose dexamethasone suppression test (DST), and brain structure in middle-aged and older adults, and whether these associations were modified by psychosocial health. MethodsFrom 2006 to 2008, 1259 participants (mean age 57.6 ± 6.4, 59.6 % female) of the population-based Rotterdam Study completed a very low-dose DST (0.25 mg) and underwent magnetic resonance imaging (MRI) of the brain. Self-reported psychosocial health (depressive symptoms, loneliness, marital status, perceived social support) were assessed in the same time period. Multivariable linear and logistic regression were used to study cross-sectional associations between cortisol response and brain volumetrics, cerebral small vessel disease markers and white matter structural integrity. To assess the effect of psychosocial health on these associations, analyses were further stratified for psychosocial health markers. ResultsCortisol response was not associated with markers of global brain structure in the overall study sample. However, in participants with clinically relevant depressive symptoms, a diminished cortisol response was associated with smaller white matter volume (mean difference: − 1.00 mL, 95 %CI = − 1.89;− 0.10) and smaller white matter hyperintensity volume (mean difference: − 0.03 mL (log), 95 %CI = − 0.05;0.00). In participants with low/moderate perceived social support compared to those with high social support, a diminished cortisol response was associated with larger gray matter volume (mean difference: 0.70 mL, 95 %CI = 0.01;1.39) and higher fractional anisotropy (standardized mean difference 0.03, 95 %CI = 0.00;0.06). ConclusionDiminished function of the HPA-axis is differently associated with brain structure in community-dwelling middle-aged and older adults with clinically relevant depressive symptoms or suboptimal social support, but not in adults without depressive symptoms or with optimal social support.

The addition of corticotropin-releasing hormone to 2-day low dose dexamethasone suppression test provides additional case detection.

PURPOSE: The diagnostic value of adding a Corticotropin-Releasing Hormone (CRH) Stimulation Test to the 2-day Low Dose Dexamethasone Suppression Test (Dex-CRH Test) has been debated in the literature. We identified 65 patients with Cushing disease (CD) and 42 patients in whom a diagnosis of Cushing disease could not be confirmed (NCD) after a minimum follow-up of 14 months who underwent the Dex-CRH test. The female sex ratio, median (range) age, and BMI were similar between the two groups. The follow-up for patients with CD and NCD was 74 (4-233) and 52 (14-146) months, respectively. Among 65 patients with CD, 5 (7.7%) had a cortisol level ≤1.4 µg/dl after LDDST but were appropriately classified as CD with a cortisol level >1.4 µg/dL at 15-min post CRH stimulation. In contrast, 3/42 patients (7.1%) in NCD had an abnormal Dex-CRH test. In only one of three patients, the LDDST was marginally normal (cortisol was 1.4 µg/dL and increased to 3.1 µg/dL 15-min post CRH). A cortisol cutoff value of >1.4 µg/dL during the Dex-CRH test provided a sensitivity of 100%, specificity of 93%, and diagnostic accuracy of 97% to diagnose CD. When patients without a Dex level were excluded (n = 74), the sensitivity did not change, but the specificity and accuracy of the Dex-CRH test increased to 97 and 99%, respectively. The Dex-CRH Test provided additional case detection in 5/65 (7.7%) patients with CD. It resulted in one false-positive case compared to LDDST. Measurement of dexamethasone improved diagnostic accuracy of the test.