Elevated ACTH Levels Research Articles

P-02 GIANT ADRENAL AND TESTICULAR MASS IN A PATIENT WITH CONGENITAL ADRENAL HYPERPLASIA

Abstract Introduction Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder characterized by impaired adrenal steroid hormone synthesis. 21-hydroxylase deficiency (21OHD) is the most common form of CAH. There are two main forms of 21OHD; salt-wasting and simple virilising. The simple virilizing form is diagnosed early in females since it has severe effects on female sexual development; however, in males, it is frequently late-diagnosed because hyperandrogenism could be overlooked. Therefore, in male patients with late diagnosis, elevated ACTH levels result in hyperplasia of ACTH-sensitive tissues in the testes, adrenal, and other sites. It is thought that adrenal rest tissues in testicular parenchyma are stimulated by their ACTH receptors and produce steroid hormones. Therefore, testicular adrenal rest tumors (TARTs) and adrenal masses occur in male patients with CAH. We present a male patient with CAH who developed complications as a consequence of a late diagnosis. Clinical Case A 35-year-old male patient from the andrology clinic was referred to our endocrinology department for incidentally detected bilateral adrenal masses. The patient had a history of precocious puberty with short stature as per his peers. Azoospermia and bilateral testicular masses were identified in the patient who was admitted to the andrology clinic with complaints of infertility. In the physical examination at the endocrinology department, the body height was 147 cm. He had generalized hyperpigmentation that was more marked on gingival mucosa and frictional sites. His blood pressure and other systems on the examination were normal. The patients’ baseline laboratory tests are given in Table 1. In hormonal assessment, cortisol levels at baseline and after the cosyntropin stimulation test were low, and 17-hydroxyprogesterone level at baseline was high. As a result of clinic and laboratory assessment, the patient was diagnosed with simple virilising CAH due to 21OHD. Then, prednisolone replacement was initiated. CT imaging revealed bilateral adrenal masses with 76*43 mm on the right and 225x135 mm on the left (Figure 1). Laparoscopic right adrenalectomy was applied, and pathology was consistent with myelolipoma. In the testicular USG evaluation, several solid lesions with irregular borders and heterogeneous echo were observed in both testicles, the largest of which was 34x16 mm on the left and 25x16 mm on the right. Bilateral adrenal and testicular masses in our patient were thought to be related to CAH. In conclusion, although newly diagnosed adult male classical CAH cases are rare, our patient was a late-diagnosed male CAH in which chronic complications developed. Early glucocorticoid treatment in CAH could protect both fertility and the adrenal gland. Therefore, the diagnosis of CAH at an early age is important. CAH should be considered in patients presenting with bilateral adrenal and testicular masses, as in our patient. Table 1:Laboratory results of the patientACTH; Adrenocorticotropic hormone, DHEA-S; Dehydroepiandrosterone sulphate; FSH; Follicle-stimulating hormone; LH; Luteinizing hormone; TSH; Thyroid-stimulating hormone

8733 Adrenal Crisis In A Patient Diagnosed With Primary Adrenal Insufficiency Following COVID-Vaccination

Abstract Disclosure: A. Hayat: None. N. Aslam: None. Primary adrenal insufficiency, or Addison's disease, is characterized by the inadequate production of cortisol and often requires lifelong hormone replacement therapy. COVID-19 vaccines have demonstrated overall safety, but this report explores a unique case of adrenal crisis post-vaccination in a patient with pre-existing adrenal insufficiency. A 38-year-old female, diagnosed with primary adrenal insufficiency, received her second dose of a COVID-19 vaccine. Within 48 hours after vaccine administration , she presented to the emergency department with severe fatigue, hypotension, nausea, and abdominal pain. Clinical examination and laboratory tests confirmed an adrenal crisis, with markedly decreased cortisol levels, hyponatremia, hyperkalemia, and an elevated ACTH level. The patient was promptly treated with intravenous hydrocortisone and saline fluids. Close monitoring of vital signs and cortisol levels was maintained, with a gradual tapering of hydrocortisone as the patient's symptoms improved. The importance of stress-dose steroids during illness or vaccination in patients with adrenal insufficiency is underscored. This case highlights that the Healthcare providers should be aware of this rare but severe complication and consider appropriate monitoring and stress-dose steroid coverage in susceptible populations. Presentation: 6/3/2024

8191 Navigating The Maze Of Adrenal Insufficiency, A Complex Case Of Late Presentation

Abstract Disclosure: K.N. Pereira: None. V. Sundaram: None. V. Mehta: None. K. Desai: None. B. Agrawal: None. Adrenal insufficiency, a rare but potentially life-threatening endocrine disorder, arises from the inadequate production or ineffective response to adrenal hormones, particularly cortisol and aldosterone. It poses diagnostic challenges, especially in individuals with intricate medical histories and manifests as either primary (Addison's disease) or secondary. The subtlety of initial symptoms often leads to a delayed diagnosis, emphasizing the importance of a high index of suspicion among healthcare providers. Timely recognition and intervention are crucial to prevent adrenal crises, which includes severe hypotension, electrolyte imbalances and life-threatening complications. This case report delves into the presentation, diagnosis, and management of primary adrenal insufficiency in a 51-year-old female with a myriad of co-morbidities who presented with persistent low blood pressure, syncope episodes and dizziness both at rest and with exertion, despite being on midodrine with systolic blood pressure readings ranging from 60s to 80s mmHg. She was also noted to be bradycardic and laboratory results showed hyponatremia, hyperkalemia, hypoglycemia and anemia. She was given prompt fluid resuscitation, stress dose steroids and fludrocortisone, leading to a remarkable improvement in blood pressure and overall clinical status. Subsequent testing showed low serum cortisol level and elevated ACTH level, confirming the diagnosis of primary adrenal insufficiency. Continued steroids resulted in significant symptomatic improvement and with no further episodes of hypotension or syncope on ensuing follow ups. This case serves as a poignant illustration for the need for a heightened clinical suspicion, as the symptoms of adrenal insufficiency can often masquerade within the intricate tapestry of comorbidities. When the utilization of midodrine, aimed at managing orthostatic hypotension, did not abate symptoms, it prompted a thorough investigation into the possibility of underlying adrenal dysfunction. This case also highlights the collaborative, multidisciplinary approach in the management of adrenal insufficiency, with endocrinology playing a pivotal role. Presentation: 6/1/2024

7438 DAX1/NR0B1 Related Adrenal Hypoplasia Congenita Without Hypogonadotropic Hypogonadism

Abstract Disclosure: R.L. Figueiredo: None. J.B. Drummond: None. A. Meireles: None. J.L. Machado: None. G. Vidigal: None. B.S. Rocha: None. Background: X-linked congenital adrenal hypoplasia (AHC) is a rare disease caused by genetic mutations in DXA1/NRB01 gene, which encodes a nuclear hormone receptor expressed in the adrenal cortex, gonads, hypothalamus and anterior pituitary gland, occurring in less than 1:12,500 live births (1,2). AHC is characterized by primary adrenal insufficiency (PAI) associated with hypogonadotropic hypogonadism (HH) and impaired spermatogenesis (oligospermia or azoospermia). Although DAX1/NR0B1 mutations can manifest with different phenotypes, HH is mostly present, which makes this present case a diagnostic challenge. Clinical case: A 23-year-old man presented with typical symptoms of adrenal insufficiency at the age of 7 (abdominal pain, dehydration, nausea, vomiting and cutaneous hyperpigmentation). Initial testing was consistent with primary adrenal failure: elevated ACTH levels (1250pg/mL, RR<46pg/mL) and very low serum cortisol (0.8mcg/dL, RR 3-20mcg/dL). Etiological investigation excluded autoimmune etiology (negative anti-adrenal and anti-21-hydroxylase antibodies) as well as adrenoleukodystrophy (normal very long chain fatty acid levels). Physical exam revealed normal virilization, testicular volume and penile length. The patient reported normal libido and sexual function. Hormonal evaluation showed normal total testosterone (424 and 713ng/dL, RR 165 to 753ng/dL) as well as calculated free testosterone (7.2 and 11.4ng/mL, RR>3.8ng/mL) levels. Abdominal CT showed signs of bilateral adrenal hypoplasia. We then proceeded to genetic testing that revealed a pathological variant c.625C>T:p (Gln 209*) in hemizygosity in exon 1 of the DAX 1/NR0B1 gene. This is a nonsense mutation that introduces a premature stop codon. This variant is not present on the global and Brazilian genetic databases (gnomAD and ABraOM) and has not been previously described in the literature. The patient is currently being treated for adrenal insufficiency with the lowest tolerated dose of prednisone (7.5mg/day) and fludrocortisone 0.1mg/day. Conclusion: Etiological investigation of patients with PAI is essential to understand the evolution of the disease, monitoring extra-adrenal manifestations and the possibility of genetic counseling for the family. An intact hypothalamic-pituitary gonadal axis should not preclude genetic evaluation for a DAX/NR0B1 mutation in patients with PAI and suspected AHC. Further studies will clarify if this specific mutation carries a genotype-phenotype correlation in patients with AHC without HH.

8282 A Diagnostically Challenging Case of Ectopic ACTH Secreting Pancreatic Neuroendocrine Tumor Presenting with Cushing’s Syndrome

Abstract Disclosure: O.A. Aluko: None. S. Patel: None. S.V. Silparshetty: None. T. Gallagher: None. Introduction: Ectopic ACTH mediated Cushing’s syndrome is an uncommon but treatable condition that poses time constrained diagnostic and therapeutic challenge due to severe morbidity as illustrated by our case below. Clinical case:A 65-year-old male was admitted with profound generalized weakness. He became restricted to wheelchair from being able to hike a trail at Yosemite national park 8 weeks prior. Recent history included hospitalization with uncontrolled diabetes and hypertension, new vertebral compression fractures, AKI, hypokalemia, proximal myopathy, anasarca, upper GI bleed and acute upper extremity DVT. Initial testing there revealed hypercortisolemia, elevated ACTH and a normal pituitary MRI. Further workup at our center revealed elevated 24hr urinary cortisol 2598 (n = 5 - 64 μg/24hr), random cortisol 55 (n= 4.2 -22.4 μg/dL) with elevated ACTH 194 (n= 7.2 - 63.3 pg/mL) consistent with ACTH dependent hypercortisolism. IPSS deferred due to AKI, underlying comorbidities and severe cervical stenosis with myelopathy. ACTH and cortisol remained elevated with an 8mg dexamethasone suppression test suggesting ectopic source ACTH. CT with contrast of chest, abdomen and pelvis showed 5mm right lower lobe lung nodule and bilateral adrenal nodularity. Bronchoscopic FNAC was negative for NET.Ketoconazole 400 mg twice daily was started pending localization of culprit lesion with improvement in 24 hr urinary cortisol to 554μg/24 hr however this was stopped within 4 weeks due to acute transaminasemia. Repeat imaging with Gallium-68 dotatate PET CT showed a 1.8 X 2.4 X 1.7 cm pancreatic mass. He underwent distal pancreatectomy with splenectomy. Pathology confirmed a 2.2cm well differentiated neuroendocrine tumor limited to the pancreas with immunohistochemistry strongly for ACTH and weakly for Gastrin. Postoperatively, patient was given hydrocortisone replacement. ACTH was 14.3 pg/mL and cortisol 6.2μg/dL a few weeks later. His diabetes, hypertension, hypokalemia, transaminasemia and proximal myopathy improved. Discussion:Ectopic ACTH mediated Cushing’s syndrome is responsible for about 5 - 20% of all Cushing’s syndrome cases. Pancreatic neuroendocrine tumor secreting Ectopic ACTH is rarer but can be aggressive. Clinical presentation can be confounding due to secretion of >1 neurohormone i.e ACTH and Gastrin in our patient. Gallium-DOTATATE PET/CT tracer has a very high sensitivity and specificity. Early use of this imaging may prevent comorbidity and mortality as surgical resection of ectopic ACTH secreting neuroendocrine tumor is first line therapy. Other diagnostic principles to consider are that severely elevated ACTH levels correlate only with a pituitary macroadenoma, IPSS is invasive and has relative contraindication in sick patients and Desmopressin stimulation test is not widely available. Presentation: 6/1/2024

8014 Cushing’s Syndrome: Two Sides of The Spectrum

Abstract Disclosure: M. Aguilera: None. A. Vu: None. J. Shakil: None. R. Al-Ward: None. Introduction: Cushing’s syndrome (CS) is a rare condition with an annual incidence of 2-8 per million. Endogenous CS is mainly due to corticotroph adenoma of the pituitary followed by excessive glucocorticoid production from adrenal and ectopic sources. CS has significant morbidity and mortality hence the need for timely diagnosis. The varied presentations often pose great challenges in identifying the source of hypercortisolism. We present two unusual cases of CS with distinct clinical presentations and atypical laboratory profiles. Case 1: 25-year-old male with no medical history presented with 9 months of facial puffiness, weight gain, fluid retention, hypertension and blurred vision. Physical examination revealed round facies, bilateral supraclavicular fat pads and wide abdominal striae. Laboratory workup showed markedly elevated ACTH 537 pg/mL [7.2-63 pg/mL], serum cortisol 8.5 ug/dL [6.2-19.4 ug/dl], 24-hour urine free cortisol (UFC) 30 [5-62 ug/24H] and normal late-night salivary cortisol (LNSC). Repeat workup a month later showed serum cortisol of 56ug/dL, ACTH 874 pg/dL, 24-hour UFC of 11880ug/24H and elevated LNSC. Pituitary MRI showed a large heterogenous 3.1 cm partially cystic sellar mass with suprasellar extension. Due to significantly elevated ACTH and short duration of symptoms, we suspected an ectopic source. Due to initial negative testing, except for high ACTH level, a silent corticotroph adenoma was also considered. The patient underwent transsphenoidal resection resulting in significant decrease of cortisol and ACTH postoperatively. Pathology showed a corticotroph adenoma with Ki-67 index of <1%. Case 2: 47-year-old woman with medical history of obesity, polycystic ovary syndrome and a stable 1 cm lung nodule since 2020, presented with fluid retention, worsening acne and resistant hypertension over a 1-year period. She required hospitalization for hypertensive emergency and hypokalemia. Laboratory data showed morning serum cortisol 28 ug/dL, ACTH of 90.1 pg/mL, 24-hour UFC 346 ug/24H, elevated LNSC on two occasions and cortisol 24.3 ug/dl after a 1mg dexamethasone suppression. MRI did not show a pituitary mass. PET dotatate scan revealed a tracer avid 1 cm right upper lobe pulmonary nodule. She underwent a right upper lobe lobectomy, resulting in a significant decrease in cortisol and ACTH levels on postoperative day 1. Pathology confirmed a typical carcinoid tumor. Discussion: High ACTH levels and a short symptom duration often point to ectopic production, paraneoplastic syndromes or corticotroph carcinomas. Cushing's disease typically exhibits mildly elevated ACTH levels, but our cases deviate from this norm, complicating source identification. This atypical presentation highlights the complexity of Cushing's syndrome, challenging conventional diagnostic paradigms. Presentation: 6/1/2024

8365 Bilateral Adrenal Hemorrhage Unveiling Adrenal Metastases In A Patient With Retroperitoneal Sarcoma

Abstract Disclosure: R.J. Shah: None. A.C. Goldberg: None. S. Jasim: None. Introduction: Metastatic disease to the adrenal gland is the most commonly occurring malignancy of the adrenal glands. Adrenal hemorrhage (AH) however is a rare but potentially fatal manifestation of malignancy. This case report highlights the unusual presentation of retroperitoneal sarcoma, manifesting as bilateral adrenal hemorrhage in the context of underlying metastases. Case Presentation: A 53-year-old man presented with a 4-week history of fatigue, intermittent abdominal pain radiating to the back, and vomiting. CT revealed bilateral adrenal masses measuring up to 8.5cm on the left side, with Hounsfield units (HU) 27, and 5.9cm on the right, HU 27, consistent with large areas of bilateral adrenal hemorrhage later confirmed on MRI. Biochemical evaluation included ACTH-stimulated cortisol, which was borderline at 17.4mcg/dl (recommended above 18-20mcg/dl), with a significantly elevated ACTH level of 103.8pg/nl (reference range 7.0-63.0pg/ml). Plasma metanephrines, electrolytes, aldosterone, and DHEA-S were normal. Although hemodynamically stable, he was started on prednisone 5mg daily as he was at high risk for primary adrenal insufficiency (AI). He was referred to endocrine surgery and further workup with PET/CT demonstrated a new FDG-avid periaortic retroperitoneal mass, with an interval increase in the size of the adrenal masses and development of hypoattenuating lesions in the kidneys and pancreas favoring aggressive metastatic disease. He underwent biopsy of the retroperitoneal mass, and pathology was consistent with high-grade sarcoma. Oncology started treatment with dexrazoxane and doxorubicin. His adrenal masses remained unchanged in size, and the patient died related to rapid progression of disease. Discussion: Spontaneous bilateral adrenal hemorrhage is rare with a reported incidence of 0.14 to 1.8%. Although most cases have been associated with sepsis, anticoagulation, hematologic disorders and trauma, it is important to maintain a high level of suspicion for underlying adrenal tumors and metastatic disease. AH can be a diagnostic challenge because of its non-specific presentation, and imaging is vital for timely recognition. Patients with bilateral AH should be managed with corticosteroids to avert AI-related fatalities. Presentation: 6/1/2024

Effects of antidepressant on FKBP51 mRNA expression and neuroendocrine hormones in patients with panic disorder

ObjectiveThe purpose of this study was to investigate the effects of escitalopram on the peripheral expression of hypothalamic-pituitary-adrenal (HPA) axis-related genes (FKBP51, HSP90, NR3C1 and POMC) and HPA-axis hormones in patients with panic disorder (PD).MethodsSeventy-seven patients with PD were treated with escitalopram for 12 weeks. All participants were assessed for the severity of panic symptoms using the Panic Disorder Severity Scale (PDSS). The expression of HPA-axis genes was measured using real-time quantitative fluorescent PCR, and ACTH and cortisol levels were measured using chemiluminescence at baseline and after 12 weeks of treatment.ResultsAt baseline, patients with PD had elevated levels of ACTH and cortisol, and FKBP51 expression in comparison to healthy controls (all p < 0.01). Correlation analysis revealed that FKBP51 expression levels were significantly positively related to cortisol levels and the severity of PD (all p < 0.01). Furthermore, baseline ACTH and cortisol levels, and FKBP51 expression levels were significantly reduced after 12 weeks of treatment, and the change in the PDSS score from baseline to post-treatment was significantly and positively related to the change in cortisol (p < 0.01).ConclusionsThe results suggest that PD may be associated with elevated levels of ACTH and cortisol, and FKBP51 expression, and that all three biomarkers are substantially decreased in patients who have received escitalopram treatment.

Corticotropin-producing pheochromocytoma in multiple endocrine neoplasia type 1

A clinical case of a man 66 y.o. who was diagnosed with hormone-inactive pituitary macroadenoma complicated by corneal erosion and partial atrophy of the optic nerve of the left eye due to exophthalmos. The increase in prolactin level was regarded due to a «stalk-effect». The patient underwent a transnasal pituitary adenomectomy with subsequent regression of symptoms. After 4 years, against the background of a new coronavirus infection, increasing general weakness, headaches, a crisis increase in blood pressure and tachycardia attacks appeared. Computed tomography (CT) accidentally revealed an adrenal incidentaloma, in laboratory tests - hypercortisolism, elevated ACTH levels, hypokalemia, hyperglycemia, increased levels of metanephrine and normetanephrine. The patient developed acute steroid psychosis, after which an adrenalectomy with a tumor was performed, a pheochromocytoma was histologically confirmed. After surgery, there was a regression of symptoms, the development of adrenal insufficiency with reduced levels of ACTH and cortisol. Upon further examination, a polynodose euthyroid goiter was established, the biopsy of the nodes - Hashimoto's thyroiditis (Bethesda II). Meanwhile, primary hyperparathyroidism was detected. According to ultrasound, scintigraphy with Ts99m-Technetril and CT revealed an increase of left parathyroid gland. A bilateral revision of the neck, removal of the right upper and left upper parathyroid adenomas were performed. In the postoperative period, the levels of calcium and parathyroid hormone were normalized. Given the presence of a combination of multiple tumors of the endocrine system (primary hyperparathyroidism, corticotropin-producing pheochromocytoma, hormone-inactive pituitary macroadenoma, polynodose euthyroid goiter), the MEN1 syndrome was clinically established. The study of 2 and 10 exons of the MEN1 gene revealed no mutations, which does not exclude the presence of a hereditary syndrome. The patient continues observation. In the available literature in Russian and English languages the case of ACTH pheochromocytoma as part of the MEN type 1 syndrome have not been found. Therefore, we consider the presented case to be the first one.

FRI212 Adrenalitis Caused By Proteus Mirabilis In An Immunocompetent Patient

Abstract Disclosure: J.O. Abdelkarim: None. U. Tarabichi: None. M. Jakoby: None. Infectious adrenalitis with Mycobacterium tuberculosis remains the leading cause of primary adrenal insufficiency in developing countries, but the incidence of adrenalitis from infection with other bacterial species is quite low. We present a patient with radiographic evidence of adrenalitis during an infection with Proteus mirabilis that resolved after antimicrobial treatment.An 86-year-old male with an indwelling Foley catheter presented to the hospital for evaluation of abdominal pain and distension. The patient was afebrile and normotensive. Examination was notable for a distended bladder and obstructed urinary catheter. Computed tomography (CT) revealed a dense right lower lobe infiltrate and bilaterally enlarged, hypointense adrenal glands with irregular margins. Radiographic findings were new compared to a CT scan obtained approximately 10 weeks before admission to hospital. Turbid and malodorous urine was drained after replacement of the patient’s urinary catheter, and urine culture grew &amp;gt; 105 CFU/mL Proteus mirabilis. Antibiotics were dosed before blood cultures were drawn, and no organisms were grown from blood cultures. Since there was no clinical or biochemical evidence (e.g. hyponatremia or hyperkalemia) of primary adrenal insufficiency, an ACTH stimulation test was deferred. The patient responded well to replacement of his urinary catheter and antibiotics and was discharged to his extended care facility three days later. A CT scan obtained 10 days after treatment showed resolution of the changes to the patient’s adrenal glands observed on admission imaging.The radiographic changes are most plausibly due to P. mirabilis bacteremia and adrenalitis. The patient had urine culture confirmed infection with P. mirabilis and radiographic evidence of disseminated infection in the right lung and adrenal glands. Adrenal enlargement is well described in cases of acute M. tuberculosis adrenalitis, and radiographic changes of adrenalitis resolved after successful treatment of the patient’s infection. P. mirabilis has been documented as an etiology of Waterhouse-Friderichsen syndrome and cultured from an adrenal abscess. Blood cultures in this case were almost certainly negative due to timing relative to initial antibiotic doses. Injury to the adrenals in bacterial adrenalitis is thought to occur due to multiple mechanisms including direct infection of the glands, endotoxemia, vasculitis, and disseminated intravascular coagulation (DIC). Hemorrhage appears to occur in about 60% of cases. Elevated ACTH level is postulated as a factor predisposing to adrenal hemorrhage, and this prompted deferral of stimulation testing to evaluate adrenal function since there was no clinical evidence of primary adrenal insufficiency. Early management of the patient’s infection likely prevented the occurrence of adrenal insufficiency and deterioration of his clinical status. Presentation: Friday, June 16, 2023

FRI245 Non-classic CAH Presenting As Bilateral Adrenal Incidentalomas

Abstract Disclosure: Y.A. Chin: None. T. Puar: None. T. King: None. Introduction: Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is an autosomal recessive disorder. Non-classic CAH usually presents in late childhood or asymptomatic may remain undiagnosed. Adrenal incidentalomas have been reported as a presentation of CAH. Clinical Case: A 56-year-old man presented with a 4-day history of epigastric pain associated with chest discomfort and diaphoresis. There was no postural giddiness, vomiting, paroxysm or constitutional symptoms. He was a smoker, his parents were non-consanguineous and he had fathered 2 children. He was tachycardic at 114 bpm, but normotensive (129/89 mmHg) with no postural hypotension and no abnormal pigmentation. He had evidence of heart failure with bibasal crepitations and pedal oedema. Secondary sexual characteristics were normal and testicular volume was 15 mls bilaterally with no palpable mass. CT abdomen showed grossly enlarged bilateral adrenal glands with heterogenous nodular appearance with several focal hypodense cystic components, with absolute washout &amp;lt;60%. Biochemistry was consistent with primary adrenal insufficiency (PAI); 8am serum cortisol 188 nmol/L, with peak cortisol post 250mcg synacthen of 195 nmol/L. Serum ACTH was elevated at 254.6 ng/L, aldosterone and renin were normal and 24hr urinary normetanephrine was mildly elevated at 1982 nmol/d (NR 600-1900 nmol/d). Echocardiography revealed severe global hypokinesia (EF 20%) but myocardial perfusion imaging was negative for ischemia. In view of suspicion for tuberculosis, malignancy or infiltrative disease, CT guided adrenal biopsy was performed. Histology showed hyperplastic adrenal cortex with lipofuscin pigments, focal lymphohistiocytic infiltrates. No lymphoplasmacytic infiltrate with IgG 4 plasma cells, granuloma, malignant cells or amyloid deposits were seen. Serum 17-OHP level later came back elevated at 39.7 nmol/L (NR 1.8-10.4 nmol/L). DNA sequencing of CYP21 revealed compound heterozygous mutations in c.292+1G&amp;gt;A and c.518T&amp;gt;A, both of which have been reported to be causative of CAH. He was transitioned from stress dose to physiological glucocorticoid replacement and ACTH normalised on subsequent outpatient visits. Follow up imaging after 6 months and 2 1/2 years revealed no change in size or morphology of the adrenal glands. Follow up echocardiography showed no improvement in ejection fraction despite intensive heart failure treatment. Conclusion: Nodular adrenal hyperplasia is well described among CAH individuals, especially in those with inadequate glucocorticoid replacement and chronically elevated ACTH levels. There was no change in size of the adrenal lesions despite adequate glucocorticoid replacement. Improvement of cardiac function with glucocorticoid replacement has been reported in paediatric patients with CAH, but our case did not show any improvement on serial echocardiography. Presentation: Friday, June 16, 2023

An unusual cause of adrenal insufficiency with elevation of 17-hydroxyprogesterone: case report

BackgroundWe present an intriguing case of primary adrenal lymphoma, with associated primary adrenal insufficiency (PAI), in a patient presenting a transitory partial 21-hydroxylase deficiency during the active phase of the adrenal disease.Case presentationAn 85-years old woman was referred because of worsening asthenia, lumbar pain, generalized myalgia and arthralgia. During investigations a computed tomography (CT) scan evidenced two large bilateral adrenal masses, highly suspicious for primary adrenal tumor. The hormonal assessment revealed very low levels of morning plasma cortisol and 24-h urinary cortisol, elevated ACTH levels with low plasma concentration of aldosterone, pointing to the diagnosis of PAI. After diagnosis of PAI our patient started glucocorticoid and mineralcorticoid replacement therapy with clinical benefit. In order to further characterize the adrenal lesions, adrenal biopsy, was performed. The histology revealed a high grade non-Hodgkin lymphoma with an immunophenotype consistent with intermediate aspects between diffuse large B-cell and Burkitt lymphoma, with a high proliferation index (KI-67 > 90%). The patient received chemotherapy with epirubicin, vincristine, cyclophosphamide, and rituximab, associated with methylprednisolone that resulted in a complete clinical and radiological remission within one year. After 2 years from the diagnosis and a total of 6 cycles of rituximab, the patient was in good clinical condition and was taking only the replacement therapy for PAI. The patient initially presented also a slight increase of 17-hydroxyprogesterone (17-OHP) for age that normalize after resolution of lymphoproliferative disease.ConclusionsIn the presence of bilateral adrenal disease and/or in the presence of signs and symptoms of PAI clinicians must exclude the presence of PAL. The evidence of elevated ACTH-stimulated 17-OHP levels also in patients with other adrenal masses, together with the detection of elevated basal 17-OHP levels in our patient make it more plausible, in our view, an effect of the lesion on the “healthy” adrenal tissue residue than a direct secretory activity by the adrenal tumor.

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.

FGF23-related hypophosphatemia in a patient with small cell lung cancer: a case report and literature review.

Although there are a few case reports of patients with small cell lung cancer developing hypophosphatemia, detailed information on this condition is scarce. A 52-year-old patient with advanced stage small cell lung cancer developed hypophosphatemia (1.1 mg/dL) during chemotherapy. A reduced level of the tubular reabsorption of phosphate concomitant with an inappropriately elevated level of fibroblast growth factor (FGF) 23 (48.4 pg/mL) was noted, leading to the diagnosis of FGF23-related hypophosphatemia. Laboratory data also showed hypercortisolemia with an elevated ACTH level and hyponatremia with an inappropriately unsuppressed level of antidiuretic hormone (ADH). These data suggested the overproduction of FGF23 in addition to ACTH and ADH. Because the octreotide loading test did not present a suppressive effect on ACTH or FGF23 levels, the patient was treated with phosphate supplementation, active vitamin D and metyrapone, which partially improved the serum phosphate and cortisol levels. Even after two subsequent courses of chemotherapy, the small cell lung cancer progressed, and the FGF23 level was further elevated (83.7 pg/mL). Although it is very rare, FGF23-related hypophosphatemia is one of the hormonal disturbances that could be observed in patients with small cell lung cancer. This article reviews similar clinical conditions and revealed that advanced states of malignancy seemed to be associated with the development of renal wasting hypophosphatemia, especially in lung cancer and prostate cancer. Therefore, the parameters related to hypophosphatemia should be monitored in patients with advanced small cell lung cancer to prevent the development of hypophosphatemic osteomalacia.

PMON94 Collision tumor with Rathke cleft cyst and co existing Cushing's disease

Abstract Introduction - Collision tumors, i.e., co-occurring distinct histopathological lesions are rare. We present a case of a 48-year-old female present with co-existing Rathke cleft cyst (RCC) and pituitary adenoma with Cushing disease. Case - 48-year-old female presented for evaluation of an incidental sellar mass with enlarged pituitary noted on MRI brain. The patient complained of symptoms of mental fogginess, confusion, intermittent dizziness for the last 1 year. The patient had complained of easy bruising with no reported weight gain, change in facial appearance, proximal muscle weakness. MRI brain showed mildly enlarged pituitary measuring 13 mm with RCC.Past medical history was significant for recent-onset Type 2 Diabetes and Hypertension. The examination was unremarkable with no signs of Cushing's syndrome. Lab work showed elevated ACTH of 51 pg/ml (10-48) with AM cortisol level of 14.7 mcg/dl (6- 18.4). IGF-1 levels elevated at 307 ng/ml (77- 220). LH, FSH, FT4, prolactin levels were normal. Given elevated ACTH levels, further testing showed elevated midnight salivary cortisol at 0.22 and 0.239 mcg/dl (0.010-0.090), elevated 24-hour urine cortisol 141 ug/ 24 hrs. (6- 44), absence of suppression with 1 mg dexamethasone with cortisol 12.4 mcg/dl (&amp;lt; 1.8), ACTH 123 pg/ml (10-48) with dexamethasone levels 432 ng/dl (140- 295). Lab work was consistent with ACTH-dependent hypercortisolism. MRI pituitary showed 7.5×7.8 mm RCC.8 mg dexamethasone suppression test and CT chest, abdomen, and pelvis were performed to differentiate between ectopic Cushing's and Cushing's disease. Cortisol levels suppressed greater than 50% after 8 mg dexamethasone from baseline cortisol – 17.7 mcg/dl and ACTH 67 pg/ml to cortisol 3.4 mcg/dl and ACTH – 34 pg/ml with dexamethasone levels of 3120 ng/dl (1600–2850). CT chest abdomen, pelvis showed no evidence of bronchial carcinoid or other potential lesions. With neuroimaging findings and biochemical confirmation of Cushing's disease, the patient underwent transsphenoidal resection. Discussion – The association between RCC and pituitary adenoma was found in 0.5–1.9% cases per literature review1, co-occurrence with ACTH producing pituitary adenoma being rarer. The diagnosis of collision tumors can be challenging as the most common presentation on imaging is a cystic mass. Appropriate biochemical testing is indicated based on clinical presentation, initial laboratory testing, and level of suspicion. Elevated ACTH levels along with diabetes and hypertension led to a diagnosis of Cushing's disease in our patient with the initial presentation of an incidental RCC. The knowledge about collision tumors is important, especially in unusual presentations as in our case. References Sagan KP et al. Cushing's Syndrome in a patient with Rathke's cleft cyst and ACTH cell hyperplasia detected by 11C-Methionine PET Imaging-A Case Presentation. Front Endocrinol (Lausanne). 2020; 11: 460. Published 2020 Jul 22. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

PMON129 Pituitary Adenoma Co-Secreting GH, Prolactin and ACTH

Abstract Background Pituitary adenomas co-secreting GH, Prolactin and ACTH are rare. Clinical Case A 38-year-old male with a past medical history of depression and type 2 diabetes mellitus was seen in the endocrinology clinic for an evaluation of acromegaly. In the preceding four years, the patient had experienced an enlargement of his hands and feet, hyperhidrosis, development of an underbite, snoring, daytime somnolence, erectile dysfunction, headaches, and blurry vision. His visual fields were normal. Physical exam: BP 137/85, BMI 39 kg/m2. He had coarse facial features, acral changes of his hands and feet, and wide spacing of his teeth. There was a notable absence of facial plethora, abdominal obesity with thin extremities, proximal muscle weakness, purple abdominal striae, and galactorrhea. Initial laboratory results: GH 16.9 ng/mL (0.05-3 ng/ml), IGF-1 1,109 ng/mL (82-242 ng/mL), Prolactin (PRL) 96.9 ng/ml (5-20 ng/ml), testosterone 34 ng/dL (200-1000 ng/dL), LH 2.3 miu/ml (1.4–12 miu/ml), FSH 4.8 miu/ml (1.5-12 miu /ml), ACTH 197.6 pg/mL (7.2- 63.3 pg/mL), 0800 cortisol 16.2 ug/dL (5-29 ug/dL), 24-hour urine free cortisol 56.84 mcg (3.5-40 mcg), HS salivary cortisol 0.242 (&amp;lt;0.359 ug/dL), overnight 1 mg Dexamethasone suppression test cortisol 6.9 mcg/dL (&amp;lt; 1.8 mcg/dL), normal Free T4 and TSH, and A1c 9.7%. A pituitary MRI revealed a 3.9 cm lobulated, intra and supra-sellar mass with mass effect on the optic chiasm and 75% encasement of the left supra-clinoid internal carotid artery. Neurosurgery performed an endoscopic, endonasal partial resection of the pituitary tumor. The histology was diagnostic of an adenoma, and immunohistochemical staining was positive for GH and PRL, but not ACTH. Post-op lab results: GH 1.07 ng/ml, IGF-1 353 ng/ml, PRL 9.6 ng/ml, testosterone 41 ng/dL, ACTH 68.2 pg/ml, cortisol 4.5 ug/dL, 24-hr urine free cortisol 8 mcg, HbA1c 5.7%. Discussion The intent of this case presentation is to report the rare finding of a pituitary tumor co-secreting GH, ACTH, and Prolactin. The diagnosis of acromegaly was confirmed by significant elevations of GH and IGF-1. The diagnosis of subclinical Cushing's disease was confirmed by elevated ACTH level, 24-hr urine free cortisol, and failed dexamethasone suppression test. The elevated PRL may have been due to tumor PRL secretion or stalk effect. The reduction of these parameters after surgery corroborated the presence of pleurihormonal secretion. This patient's findings support screening for co-secretion of multiple pituitary hormones in patients with acromegaly. Reference Pleurihormonal ACTH-GH Adenoma: Case Report and Systematic Literature Review World Neurosurg 2018 114: 158-164 Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

ODP055 The methylation pattern of a unique Bilateral para-overian Adrenal Rest Tumor in a girl with Nicotinamide Nucleotide Transhydrogenase mutation

Abstract Background Patients with NNT (Nicotinamide Nucleotide Transhydrogenase) gene mutations, a rare cause of glucocorticoid and mineralocorticoid deficiency require hormone replacement therapy. Adrenal Rest Tumor (ART) in females, reported so far only in noncompliant patients with congenital adrenal hyperplasia and elevated ACTH levels, is very rare (&amp;lt;20 cases world-wide). This study characterizes the pathophysiology, the molecular ontogeny and methylation analysis of a unique ART in a female with adrenal failure due to the G200S mutation in NNT Clinical presentation and Method: A 15-year-old girl, with homozygous G200S NNT-mutation followed for adrenal insufficiency reappeared to follow-up with severe virilization and elevated serum testosterone (28.3 nmol/l) and ACTH (&amp;gt; 1500 pmol/l). Pelvic MRI and Ultrasound demonstrated one sided paraovarian round tumor with pathological vascularization. Laparoscopic exploration revealed bilateral para ovarian mesosalpinx masses involving the serosa of the Fallopian tube, (3 and 1 cm in diameter). The testosterone level normalized within one day after surgical removal of those masses (0.2 nmol/l). Results Histopathology demonstrated a pattern of adrenal rest tissue with strong intracellular positive staining for adrenal markers such as SF-1, calretinin, MART1, inhibin and the pituitary marker ACTH. The staining for ovarian characteristic markers such as PAX 8 was negative. Studying mRNA extracted from the tissue by RT-PCR revealed the positive Gene expression of Cyp17a1, Cyp21a2 and Mc2r cDNA but not Pomc suggesting adrenal but not pituitary origin of the tissue. We further profiled the epigenomic profile of several adrenal rest tumors from both ovarian and testes origins using the Infinium Methylation EPIC array. We characterized the adrenal-specific features by comparing the tumors from the two different originating sites to published methylation array data on healthy adrenal tissue. We further investigated cancer-specific methylation changes to identify activated cancer pathways, and used the methylation arrays to identify somatic copy number alterations. Finally, we analyzed the likely developmental origin of these tumors by comparing to published methylation array data of developmental and adult reproductive tissues. Conclusion This study exemplifies severe virilization that resulted from a unique and rare type of ART in ovarian related tissue that was caused by incompliance to treatment in a patient with NNT gene mutation. The laparoscopic surgical findings indicate that imaging techniques may be insufficient in identification of such rest tumors and call for laparoscopy when clinical findings are suggestive. An early detection of this tumor could preserve fertility. Using histopathology markers cDNA studies and epigenomic profiling by methylation studies, our study shows for the first time that female ART originates from adrenal cells. The growth of a functional androgen producing "tumor" indicates that functional NNT protein is NOT required for androgen synthesis in contrast to glucocorticoids and that a zona reticularis similar tissue in ART is responsive to ACTH stimulation. Presentation: No date and time listed

RF33 | PSAT69 A Combined Candidate Gene/Whole Exome Sequencing Approach Permits a Rapid Genetic Diagnosis for &amp;gt;81% Individuals with Primary Adrenal Insufficiency.

Abstract Introduction Mutations in MC2R causing familial glucocorticoid deficiency (FGD), a rare form of primary, isolated adrenal insufficiency, were first published in 1993, discovered by candidate gene sequencing (CGS). Through advances in genetic techniques from homozygosity mapping to whole exome sequencing (WES) we have linked a further five genes to adrenal insufficiency and, in conjunction with other groups, this has expanded the number of monogenic causes for isolated or syndromic adrenal insufficiency to &amp;gt;25. Patients and Methods Over the last 30 years over 400 individuals with suspected FGD, from 31 different countries, have been referred to our centre for genetic testing, ranging in age from neonates to individuals in their eighties. All cases had low or undetectable serum cortisol usually paired with an elevated plasma ACTH level. Our strategy for sequencing has evolved over time and we now routinely sequence the small, frequently mutated, candidate genes by Sanger sequencing (MC2R, MRAP, STAR and CYP11A1) before proceeding to WES as the most cost-effective route to a genetic diagnosis. In total, 369of the 400 individuals have been fully characterised either by CGS or WES. For CGS, sequences were analysed by alignment to reference sequences using BioEdit software and for WES variant call files were initially analysed using Ingenuity Variant Analysis package and/or examination of BAM files, using the Integrative Genomics Viewer, to detect exonic deletions. Rare, synonymous or predicted benign variants were further tested by an in vitro splicing assay using the pET01 vector (MoBiTec) Results In 308/ 369 individuals we found a definitive diagnosis in a gene known to be causal for adrenal insufficiency, giving a success rate of &amp;gt;81%, and identified 15 novel mutations. The aetiologies of diagnosed cases were as follows; MC2R (22%), MRAP (17%), NNT (15%), STAR (9%), CYP11A1 (7%), with the remaining 30% due to a further 13 genes. Founder effects were clear for variants in some genes/populations, whereas in others hotspot mutations were present in multiple ethnicities. Examples include the previously described S74I in MC2R and rs6161 in CYP11A1 in the UK population, P24Rfs*4 in MCM4 in Ireland, R188C in STAR in Canada, and newly discovered associations with T731= in NNT in Sudan and R222Q in SGPL1 in Saudi Arabia. Whereas MRAP splice mutations commonly seen at the exon 3/intron 3 junction were present in individuals from many countries. The work has also highlighted a number of causal synonymous and predicted benign variants that result in splicing defects. Conclusion The use of CGS/WES now permits a rapid genetic diagnosis for &amp;gt;83% individuals with PAI improving tailored patient management. For the remaining patients it is unclear whether they have unconventional mutations in known genes or if there are further gene defects to be discovered. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Monday, June 13, 2022 1:24 p.m. - 1:29 p.m.

ODP387 Hemihypertrophy: A Rare Clinical Presentation of Cushing's disease

Abstract Background Hemihypertrophy is a rare clinical presentation of Cushing's disease. It has been described in three newborns with massive enlargement of adrenal glands in presence of other congenital abnormalities and in a 17-year-old female with pituitary adenoma with a genetic diagnosis of Beckwith Weidman syndrome. We describe a case of Cushing's disease with lower extremity hemihypertrophy in the absence of features suggestive of an underlying syndrome. 1,2 Clinical Case: A 12-year-old male with no significant past medical history presented with poor growth and rapid weight gain. In addition, he had hemihypertrophy of left lower extremity interfering with his physical activity. Physical exam showed Tanner Stage 1 for pubic hair and testicular volume of 4 ml bilaterally, with no signs of hirsutism, bruising or purplish striae. Initial work up showed normal thyroid hormone and growth factor levels. Midnight salivary cortisol levels were 238 ng/dl and 51 ng/dl respectively (range &amp;lt;100 ng/dl). One mg dexamethasone suppression test showed suppressed cortisol level of 1 mcg/dl. At the subsequent visit seven months later, he had gained 13.8 kg and grown 0.9 cm in height. Physical exam showed facial plethora and buffalo hump, which had not been present at the initial visit. Left and right leg circumference above the knee were 22 inches and 20 inches respectively. Repeat midnight cortisol levels on two separate occasions were 251 ng/dl and 441 ng/dl respectively. Repeat 1 mg dexamethasone suppression test showed suppressed cortisol levels of 1.2 mcg/dl. Because of clinical picture consistent with Cushing syndrome and elevated salivary cortisol levels, 24-hour urine cortisol levels were ordered that were 145 mcg and 276 mcg/24h respectively (range 1-45 mcg/24hours). ACTH was elevated at 65 pg/ml. CT scan of abdomen and pelvis was normal. Left leg ultrasound was normal. MRI of brain showed a 4 mm hypoenhancing lesion in the pituitary gland to the left of midline. A peripheral DDAVP stimulation test showed elevated ACTH and cortisol levels suggestive of pituitary origin. MRI of legs showed asymmetric fat deposition causing hemihypertrophy. Patient underwent transsphenoidal resection of pituitary adenoma with postoperative remission (postop cortisol nadir &amp;lt;1 mcg/dl). At follow up visit after surgery, patient had lost 0.2 kg, buffalo hump had disappeared, and left leg circumference had slightly improved. Genetic testing ispending. Conclusion This case demonstrates that hemihypertrophy can be a presenting symptom of Cushing's disease.

ODP621 Hypertension with Hypokalemia in Pregnancy? Think "Cushing's Syndrome"

Abstract Introduction Pregnancy is uncommon in women with Cushing's syndrome (CS) as hypercortisolism and hyperandrogenism suppress gonadotropins leading to anovulatory cycles. Such pregnancies carry a higher rate of fetal morbidity and mortality. Therefore, it is of paramount importance to diagnose and treat CS in pregnancy. The diagnosis of CS in pregnancy is challenging due to the physiologic changes of the hypothalamic-pituitary-adrenal axis during pregnancy. We describe a case of CS in pregnancy that was a successfully treated with surgery. Case description An asymptomatic 39-year-old pregnant female patient with gestational hypertension was admitted to the hospital after she was found to have uncontrolled hypertension (while on 3 anti-hypertensive medications) and severe hypokalemia with potassium level of 2.8 mEq/L. She was 14 weeks pregnant at the time. She has a family history of primary aldosteronism in her father successfully treated with adrenalectomy at the age of 60. Her work up included blood work (done at 13: 42) which showed sodium level of 146 mEq/L, plasma aldosterone concentration of &amp;lt;1 ng/dL, plasma renin activity of 1.0 ng/mL/hr, total testosterone of 46 ng/dL, DHEA-S of 31 mcg/dL, plasma metanephrines &amp;lt;50 pg/mL, 24-hour urine metanephrines 70 ug, 24-hour urine normetanephrines 164 ug/24 hrs, ACTH 5 pg/mL, and cortisol 28.2 mcg/dl. MRI abdomen without contrast showed a 3.5×3.0×4.2 cm left adrenal nodule consistent with adenoma. Patient was diagnosed with non-ACTH dependent subclinical CS based on her elevated cortisol and low ACTH levels. She underwent left laparoscopic adrenalectomy and was discharged on oral hydrocortisone. Pathology showed adrenal cortical adenoma. Her blood pressure normalized shortly after surgery and her anti-hypertensive medications were stopped. Discussion Pregnancy is associated with multiple changes in the hypothalamic-pituitary-adrenal axis making diagnosis of CS in pregnancy challenging. Those changes include increased Cortisol binding globulin production leading to increased serum cortisol level and lack of suppression with Dexamethasone beside placental production of CRH and ACTH, all leading to increased salivary and urinary free cortisol levels, as well. This case of hypertension and hypokalemia in pregnancy presented a diagnostic dilemma. Furthermore, the clinical presentation was confounded by a family history of primary aldosteronism. However, the low serum ACTH level highly suggested the diagnosis of CS. Unfortunately, there are no pregnancy-specific guidelines for the diagnosis of CS. The dexamethasone suppression test is not recommended as it often yields false-positive results. The use of urinary free cortisol and late-night salivary cortisol is recommended, and the diagnosis is established when results are three to four times the upper limit of normal. ACTH levels &amp;lt;10 pg/ml are suggestive of adrenal CS. MRI without contrast can be used for imaging. To date, there have been over 260 reported cases of CS in pregnancy with more than half of them being. Presentation: No date and time listed