Elevated Adrenocorticotropic Hormone Research Articles

Pituitary Crooke cell neuroendocrine tumor of adrenocorticotropic hormone differentiation-specific transcription factor lineage: a clinicopathological analysis of six cases

Objective: To investigate the clinicopathological features of Crooke cell tumor of adrenocorticotropic hormone differentiation specific transcription factor (TPIT, also known as transcription factor 19, TBX19) lineage neuroendocrine tumors. Methods: Six cases of Crooke cell tumor diagnosed at the First Affiliated Hospital of University of Science and Technology of China, Hefei, China from October 2019 to October 2023 were collected. The clinical and pathological features of these cases were analyzed. Results: Among the six cases, one was male and five were female, with ages ranging from 26 to 75 years, and an average age of 44 years. All tumors occurred within the sella turcica. Clinical presentations included visual impairment in two cases, menstrual disorders in one case, Cushing's syndrome in one case, headache in one case, and one asymptomatic case discovered during a physical examination. Preoperative serum analyses revealed elevated levels of cortisol and adrenocorticotropic hormones in two cases, elevated cortisol in two cases, elevated adrenocorticotropic hormone in one case, and one case with a mild increase in prolactin due to the pituitary stalk effect. Magnetic resonance imaging revealed uneven enhancement of masses with maximum diameters ranging from 1.7 to 3.2 cm, all identified as macroadenomas. Microscopically, tumor cells exhibited irregular polygonal shapes, solid sheets, or pseudo-papillary arrangements around blood vessels. The cell nuclei were eccentric or centrally located, varying in size, with abundant cytoplasm. Some tumor cells showed perinuclear halo. Immunohistochemistry demonstrated diffuse strong positivity for TPIT in five cases, focal weak positivity for TPIT in one case, diffuse strong positivity for adrenocorticotropic hormone in all cases, and faint staining around the nuclei in a few cells. CK8/18 showed a strong positive ring pattern in more than 50% of tumor cells, focal weak positive expression of p53, and the Ki-67 positive index ranged 1%-5%. Periodic acid-Schiff staining revealed positive cytoplasm and negative perinuclear areas. Conclusions: Crooke cell tumor is a rare type of pituitary neuroendocrine tumors. Its pathological characteristics include a distinctive perinuclear clear zone and immunohistochemical markers, such as CK8/18 exhibiting a ring or halo pattern. This entity represents a high-risk subtype among pituitary neuroendocrine tumors, displaying a high risk of invasion and a propensity for recurrence. Accurate diagnosis is crucial for the postoperative follow-up and multimodal treatment planning.

#2026 Hypokalemia associated to neuroendocrine carcinoma of the cervix

Abstract Background and Aims Hypokalemia is one of the most common electrolyte disorders seen in clinical practice. Hypokalemia can be caused by decreased intake of potassium, redistribution of potassium (K+) in cells or by excessive gastrointestinal losses or renal losses. In this setting, hypokalemia may also be caused by the paraneoplastic production of ectopic adrenocorticotropic hormone (ACTH) by some tumors. Cancer of the uterine cervix is the fourth common cancer affecting women worldwide and the fourth most common gynecologic cancer in Spain. Neuroendocrine carcinoma of the cervix represents about 2% of all cervical neoplasms. Method We report the case of a 44-year-old Peruvian woman with hypokalemia who was diagnosed with Cushing syndrome secondary to paraneoplastic production of ACTH by neuroendocrine carcinoma of cervix. Results Patient was overweight and affected by uterine myoma and anemia without further investigations. She was admitted to our hospital due to lower back pain, leg swelling and constipation. Blood pressure was normal, chest radiography did not show abnormal findings and ECG showed the U wave. Laboratory tests at admission revealed hypokalemia (2.3 mmol/L), metabolic alkalosis, anemia (hemoglobin 9.5 g/dL), hyperkaliuria (K+ urine/Creatinine urine 70 mmol/g) with an elevated transtubular potassium gradient (TTKG=12) and normal renal function. Laboratory data are presented in Table 1. She developed hypertension in the first day of hospitalization. Renin, aldosterone and cortisol tests was performed. Hypercortisolism was observed and confirmed with 24-hour urinary cortisol excretion. Because of an elevated ACTH (263 pg/mL), pituitary magnetic resonance imaging was performed without lesions. Whole-body computed tomography revealed a cervical mass. PET scan showed pelvic, adrenal, hepatic and local lymphadenopathy activity (see Fig. 1). After the histopathological study, diagnostic of small cell neuroendocrine carcinoma of the cervix was made. Chemotherapy therapy was initiated with cisplatin/etoposide regimen. The patient decide to return to Peru because of the poor prognosis of her illness. At discharge, potassium level was 3 mmol/L despite the treatment with spironolactone, ramipril, losartan and oral potassium chloride (160 mmol). Conclusion Hypokalemia is a common clinical disorder. In some patients it may be caused by an increased mineralocorticoid activity due to ectopic ACTH-secreting tumors. Applying diagnostic algorithms to electrolyte disorders, beyond their simple treatment, can unmask secondary causes and serious diseases.

478. Elevated Plasma Adrenocorticotropic Hormone (ACTH) Levels Correlate With Reduced Suicidal Thoughts in Psychiatric Patients Relative to Control Groups, Regardless of Depression Intensity

478. Elevated Plasma Adrenocorticotropic Hormone (ACTH) Levels Correlate With Reduced Suicidal Thoughts in Psychiatric Patients Relative to Control Groups, Regardless of Depression Intensity

(PM-19) INSIGHTS INTO THE PATHOPHYSIOLOGY OF HYPERSEXUALITY: A COMPREHENSIVE LITERATURE EXPLORATION

Abstract Introduction Hypersexuality or Compulsive Sexual Behavior Disorder (CSBD) is characterized by a spectrum of sexual behaviors and fantasies marked by compulsion, obsession, and impulsivity. The pathophysiology of CSBD remains poorly understood despite the arousing of articles exploring the potential biomarkers associated with hypersexuality. Objective We aimed to review the literature regarding the investigation on CSBD pathophysiology from a neuroimaging, neuroendocrine and molecular perspective. Methods We raised papers related on neuroimaging, neuroendocrine and molecular biomarkers investigated in individuals that reached diagnosis of CSBD or similar, written in English language in the last 10 years, through PubMed, Scopus, and Web of Science with biomarkers and compulsive sexual behavior/hypersexuality key terms. Results Neuroimaging studies revealed the activation of the anterior cingulate cortex, ventral striatum, and amygdala, in individuals with CSBD. Neuroendocrine markers revealed abnormalities in the hypothalamic-pituitary-adrenal (HPA) axis, including elevated adrenocorticotropic hormone (ACTH) levels and non-suppression of dexamethasone. Findings concerning the hypothalamic-pituitary-gonadal (HPG) axis, responsible for sexual function regulation, varied among CSBD individuals, including testosterone and luteinizing hormone (LH) levels. Oxytocin levels have been noted to rise in CSBD individuals and subsequently decrease following psychotherapy. Genetic and epigenetic markers associated with CSBD suggest involvement of addiction-related genes and epigenetic modifications near the corticotropin-releasing hormone (CRH) gene. Conclusion Most of the findings point to HPA axis alterations. Molecular analysis is in the beginning, as well as more research on the HPG axis is needed. The exploration of CSBD biomarkers potentially will provide insights into its pathophysiology, diagnosis, and treatment. Financing FAPESP.

Novel co-occurrence of hypophosphatemic rickets with 46XY DSD (disorder of sex development) due to a CYP17A1 variant

17-α-hydroxylase deficiency causes a rare type of congenital adrenal hyperplasia (CAH). X-linked hypophosphatemic rickets (XLH) is a rare disorder caused by inactivating mutations in the PHEX gene. We report a novel co-occurrence of XLH with 46XY disorder of sex development due to 17-α-hydroxylase deficiency. A young child reared as a girl, presented as a toddler with genu varus, low phosphorus, normal calcium, and parathormone, and was treated as hypophosphatemic rickets. In early childhood, due to short stature and hypertension, the child was investigated for Turner syndrome. Ultrasound revealed intra-abdominal gonads and an absent uterus. The karyotype was 46XY. Investigations revealed low serum cortisol, renin, normal 17-hydroxyprogesterone, and aldosterone. A year later, a bilateral orchidectomy was performed. Two years later, she was referred to us for further management. Adrenocorticotrophic hormone (ACTH), cortisol, renin, deoxycorticosterone, and clinical exome were advised. She was lost to follow-up for 3 years. On follow-up in early adolescence, she was pre-pubertal; biochemical findings of hypophosphatemic rickets, elevated ACTH, low cortisol, and low normal aldosterone were noted. Clinical exome revealed variants in the CYP17A1 gene (homozygous) causing CAH (17-α-hydroxylase) and PHEX (hemizygous) gene causing XLH. Treatment with hydrocortisone, phosphate, cholecalciferol, and calcitriol was commenced. Hypertension is now well-controlled, but genu varus persists and may require surgical correction.

Ectopic Adrenocorticotropic Hormone Syndrome due to Pancreatic Neuroendocrine Carcinoma: A Case Report.

A 55-year-old woman presented to her primary care physician with facial and lower leg edema. After being referred to our hospital because of hypothyroidism and hypokalemia on blood tests, she also had elevated adrenocorticotropic hormone (ACTH) and cortisol levels, but a dexamethasone suppression test showed no cortisol suppression. Ectopic ACTH syndrome due to pancreatic neuroendocrine carcinoma (PNEC) was suspected. endoscopic ultrasound-guided fine-needle aspiration was performed, and a histopathological examination of the obtained specimen revealed multiple liver metastases of the PNEC. Imaging after etoposide and cisplatin therapy showed cystic changes in the primary lesions and shrinkage of the liver metastases, and the ACTH levels were within the normal range.

Early Adverse Family Experiences and Elevated Adrenocorticotropic Hormone Predict Non-Suicidal Self-Injury in Females with Non-Psychotic Mental Disorders and Suicidal Ideation.

Nonsuicidal self-injurious behavior (NSSI), prevalent in patients with non-psychotic mental disorders (NPMD), is associated with numerous adverse outcomes. Despite active research into the clinical and psychological aspects of NSSI, the underlying biological mechanisms remain obscure. Early adverse experiences are believed to induce long-lasting changes in neuroendocrine mechanisms of stress control playing a key role in NSSI development. The aim of the study was to evaluate parameters potentially predicting development of NSSI in female patients with NPMD and suicidal ideation. Eighty female patients over 18 years with NPMD and suicidal ideation (40 with and 40 without NSSI) and 48 age matching women without evidence of mental illness (healthy controls) were enrolled. Diagnostic interviews and self-report measures were used to assess childhood maltreatment, presence, frequency, and characteristics of suicidal and self-injurious thoughts and behaviors, the Beck Depression Inventory scale to assess severity of depression. Hypothalamic-pituitary-adrenal axis markers, hormones, and neurotrophic factors were measured in blood serum. The likelihood of developing NSSI in patients with NPMD and suicidal ideation was associated with early adverse family history and elevated adrenocorticotropic hormone levels. Dysregulation of hypothalamic-pituitary-adrenal axis as a result of early chronic stress experiences may represent critical biological mechanism promoting the development of NSSI behaviors in patients with NPMD.

Repeated toluene and cyclohexane inhalation produces differential effects on HPA and HPT axes in adolescent male rats

Misused volatile solvents typically contain toluene (TOL) as the main psychoactive ingredient. Cyclohexane (CHX) can also be present and is considered a safer alternative. Solvent misuse often occurs at early stages of life, leading to permanent neurobehavioral impairment and growth retardation. However, a comprehensive examination of the effects of TOL and CHX on stress regulation and energy balance is lacking. Here, we compared the effect of a binge-pattern exposure to TOL or CHX (4,000 or 8,000 ppm) on body weight, food intake, the hypothalamus-pituitary-adrenal (HPA) and hypothalamus-pituitary-thyroid (HPT) axes in male adolescent Wistar rats. At 8,000 ppm, TOL decreased body weight gain without affecting food intake. In addition, TOL and CHX altered the HPA and HPT axes’ function in a solvent- and concentration-dependent manner. The highest TOL concentration produced HPA axis hyperactivation in animals not subjected to stress, which was evidenced by increased corticotropin-releasing-factor (CRF) release from the median eminence (ME), elevated adrenocorticotropin hormone (ACTH) and corticosterone serum levels, and decreased CRF mRNA levels in the hypothalamic paraventricular nucleus (PVN). TOL (8,000 ppm) also increased triiodothyronine (T3) serum levels, decreased pro-thyrotropin-releasing-hormone (pro-TRH) mRNA transcription in the PVN, pro-TRH content in the ME, and serum thyroid stimulating hormone (TSH) levels. CHX did not affect the HPA axis. We propose that the increased HPT axis activity induced by TOL can be related to the impaired body weight gain associated with inhalant misuse. These findings may contribute to a better understanding of the effects of the misused solvents TOL and CHX.

On Primary Adrenal Insufficiency with Normal Concentrations of Cortisol - Early Manifestation of Addison's Disease.

Primary adrenal insufficiency (AI) is an endocrine disorder in which hormones of the adrenal cortex are produced to an insufficient extent. Since receptors for adrenal steroids have a wide distribution, initial symptoms may be nonspecific. In particular, the lack of glucocorticoids can quickly lead to a life-threatening adrenal crisis. Therefore, current guidelines suggest applying a low threshold for testing and to rule out AI not before serum cortisol concentrations are higher than 500 nmol/l (18 μg/dl). To ease the diagnostic, determination of morning cortisol concentrations is increasingly used for making a diagnosis whereby values of>350 nmol/l are considered to safely rule out Addison's disease. Also, elevated corticotropin concentrations (>300 pg/ml) are indicative of primary AI when cortisol levels are below 140 nmol/l (5 μg/dl). However, approximately 10 percent of our patients with the final diagnosis of primary adrenal insufficiency would clearly have been missed for they presented with normal cortisol concentrations. Here, we present five such cases to support the view that normal to high basal concentrations of cortisol in the presence of clearly elevated corticotropin are indicative of primary adrenal insufficiency when the case history is suggestive of Addison's disease. In all cases, treatment with hydrocortisone had been started, after which the symptoms improved. Moreover, autoantibodies to the adrenal cortex had been present and all patients underwent a structured national education program to ensure that self-monitored dose adjustments could be made as needed.

Association of Metabolic and Endocrine Disorders with Bovine Ovarian Follicular Cysts.

After estrus, when mature follicles fail to ovulate, they may further develop to form follicular cysts, affecting the normal function of ovaries, reducing the reproductive efficiency of dairy cows and causing economic losses to cattle farms. However, the key points of ovarian follicular cysts pathogenesis remain largely unclear. The purpose of the current research was to analyze the formation mechanism of ovarian follicular cysts from hormone and gene expression profiles. The concentrations of progesterone (P4), estradiol (E2), insulin, insulin-like growth factor 1 (IGF1), leptin, adrenocorticotropic hormone (ACTH) and ghrelin in follicle fluid from bovine follicular cysts and normal follicles were examined using enzyme-linked immunosorbent assay (ELISA) or 125I-labeled radioimmunoassay (RIA); the corresponding receptors' expression of theca interna cells was tested via quantitative reverse transcription polymerase chain reaction (RT-qPCR), and the mRNA expression profiling was analyzed via RNA sequencing (RNA-seq). The results showed that the follicular cysts were characterized by significant lower E2, insulin, IGF1 and leptin levels but elevated ACTH and ghrelin levels compared with normal follicles (p < 0.05). The mRNA expressions of corresponding receptors, PGR, ESR1, ESR2, IGF1R, LEPR, IGFBP6 and GHSR, were similarly altered significantly (p < 0.05). RNA-seq identified 2514 differential expressed genes between normal follicles and follicular cysts. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis linked the ovarian steroidogenesis pathway, especially the STAR, 3β-HSD, CYP11A1 and CYP17A1 genes, to the formation of follicular cysts (p < 0.01). These results indicated that hormone metabolic disorders and abnormal expression levels of hormone synthesis pathway genes are associated with the formation of bovine ovarian follicular cysts.

THU009 Subclinical Cushing’s Syndrome In An ACTH-secreting Pituitary Macroadenoma

Abstract Disclosure: N.G. Akabogu: None. D. Kumar: None. N. Sheung: None. A. Akofu: None. A. Uddin: None. S. Dejhansathit: None. F. Marium: None. L.G. Kurukulasuriya: None. Background: Subclinical Cushing’s syndrome (SCS) is characterized by subtle cortisol hypersecretion, which does not result in the typical signs and symptoms of Cushing’s syndrome (CS). While many of the signs and symptoms of CS are common in the general population, there are some that are discriminatory and specific for CS: supraclavicular fat pads, proximal muscle weakness, facial plethora, and violaceous striae. SCS manifests mostly as obesity, type 2 diabetes, and hypertension. Diagnosing SCS is challenging; however, the best screening test to uncover the subtle hypercortisolism is the dexamethasone suppression test (DST). Case presentation: We report a case of SCS in a 62 years old Caucasian postmenopausal patient with a medical history of total thyroidectomy for Graves’ disease, post-surgical hypothyroidism, 7.4cm right pheochromocytoma status post partial right adrenalectomy, incidentally discovered pituitary macroadenoma (during imaging to look for subarachnoid hemorrhage), untreated type 2 diabetes mellitus (A1c 6.6% and stable for 1 year before treatment), hypertension, atrial fibrillation, cerebrovascular accident, and worsening migraines. Patient’s physical exam was mostly unremarkable; she had central obesity and bilateral lower extremity swelling. Pituitary work-up showed evidence of secondary hypogonadism and secondary hypothyroidism with elevated adrenocorticotropic hormone (ACTH) of 130 (AM range: 7.2-63) and cortisol of 12.6, at 11:52AM. Further work-up for hypercortisolism revealed non-suppressed 8AM cortisol (5.83mcg/dL) on the low dose DST and 49% suppression of 8AM cortisol and ACTH on the high dose DST. 24hour urinary cortisol was normal. Patient did not perform the midnight salivary cortisol. Patient subsequently underwent trans-sphenoidal resection of the pituitary macroadenoma. Pathology analysis of the pituitary mass showed weak to moderate immunoreactivity for ACTH. Conclusion: Our patient had abnormal DST but normal 24hour urine cortisol. We may have missed her SCS if we screened her only with a 24hour urine cortisol. This confirms the fact that dexamethasone suppression test should be the first test in the evaluation of subclinical Cushing’s syndrome. Presentation: Thursday, June 15, 2023

Complete recovery after glucocorticoid replacement therapy in a case of primary adrenal insufficiency caused by adrenal tuberculosis infection.

Symptoms of primary adrenal insufficiency (PAI) are commonly nonspecific, causing the disease to be misdiagnosed or often delayed, and patients may present to the hospital with a life-threatening crisis. Previous case reports have documented that patients in this condition often require lifelong glucocorticoid replacement therapy. This study aimed to present a noteworthy outcome of PAI caused by adrenal tuberculosis infection, demonstrating complete recovery after six months of glucocorticoid replacement therapy. A 38-year-old Indonesian man presented to the endocrinology clinic in a tertiary hospital with a chief complaint of epigastric pain. The patient experienced nausea, vomiting, loss of consciousness, weight loss, excessive sweat, decreased appetite, weakness, and dizziness in the past 2 weeks. Laboratory examinations revealed hyponatremia, elevated adrenocorticotropic hormone, and suppressed morning plasma cortisol level. A non-contrast-enhanced abdominal MRI showed unilateral right-side adrenal enlargement and calcification. The patient's Mantoux test was positive. Corticosteroids and anti-tuberculosis therapy were administered. After 6 months, hydrocortisone was discontinued due to the patient's good clinical condition and normal morning plasma cortisol levels. After a 1-year follow-up, the patient remained asymptomatic with normal cortisol levels. We hypothesized several reasons for this unique outcome: (i) the patient was relatively young compared to previous cases, suggesting an adequate immune system may play a role; (ii) despite a 1-month delay in diagnosis and treatment, the absence of skin hyperpigmentation suggested an acute presentation, potentially contributing to the favorable outcome; and (iii) the absence of comorbidities potentially positively impacted the patient's outcome. Symptoms of adrenal insufficiency are often nonspecific and may only become apparent once significant damage has occurred to the adrenal gland. Clinical adjustments and a comprehensive understanding of epidemiological knowledge are necessary for diagnosing patients with endocrine diseases in limited-resource settings. Complete recovery in primary adrenal insufficiency caused by tuberculosis infection might be due to younger age, acute presentation, and absence of comorbidities.

Long-term health consequences of congenital adrenal hyperplasia.

Congenital adrenal hyperplasia (CAH) caused by 21-hydroxylase deficiency accounts for 95% of all CAH cases and is one of the most common inborn metabolic conditions. The introduction of life-saving glucocorticoid replacement therapy 70 years ago has changed the perception of CAH from a paediatric disorder into a lifelong, chronic condition affecting patients of all age groups. Alongside health problems that can develop during the time of paediatric care, there is an emerging body of evidence suggesting an increased risk of developing co-morbidities during adult life in patients with CAH. The mechanisms that drive the negative long-term outcomes associated with CAH are complex and involve supraphysiological replacement therapies (glucocorticoids and mineralocorticoids), excess adrenal androgens both in the intrauterine and postnatal life, elevated steroid precursors and adrenocorticotropic hormone levels. Alongside a review of mortality outcome, we discuss issues that need to be addressed when caring for the CAH patient including female and male fertility, cardio-metabolic morbidity, bone health and other important long-term outcomes of CAH.

Genetic and phenotypic spectrum of non-21-hydroxylase-deficiency primary adrenal insufficiency in childhood: data from 111 Chinese patients

BackgroundPrimary adrenal insufficiency (PAI) is a rare but life-threatening condition. Differential diagnosis of numerous causes of PAI requires a thorough understanding of the condition.MethodsTo describe the genetic composition and presentations...

Adrenal Hemorrhaging in a Patient with Severe Obstructive Sleep Apnea Syndrome with Elevated Plasma ACTH Levels.

Adrenal hemorrhaging (AH) is a rare condition characterized by bleeding into the suprarenal glands. A 62-year-old man with untreated obstructive sleep apnea syndrome (OSAS) was admitted to our hospital complaining of abdominal stiffness. He was diagnosed with left-sided AH and underwent adrenalectomy. Pre- and post-surgery, elevated plasma adrenocorticotropic hormone (ACTH) levels were observed. However, Cushing's syndrome and adrenal insufficiency were negative, and nasal continuous positive airway pressure (CPAP) normalized the plasma ACTH levels. Elevated ACTH levels are reportedly present in patients with OSAS. ACTH may be associated with the development of AH through the change in blood supply and other mechanisms.

Ectopic Cushing’s Syndrome as the First Presenting Sign of Small Cell Lung Carcinoma

A 67-year-old man with a history of hypertension, hyperlipidemia, coronary artery disease, and former smoking presented with fatigue, lower extremity edema, and a new tremor over the course of one month. Workup was notable for hypokalemia, metabolic alkalosis, and extremely elevated adrenocorticotropic hormone (ACTH) and cortisol levels. He was ultimately diagnosed with ectopic Cushing’s syndrome (CS) secondary to new metastatic small cell lung carcinoma. About 5-10% of CS cases are caused by ectopic ACTH production. The most commonly implicated malignancies are small cell lung cancer (SCLC) and neuroendocrine tumors, with SCLC accounting for up to three-fourths of cases. ACTH production is a poor prognostic sign in SCLC, associated with more extensive disease and decreased response to first-line treatment. Tumor-associated ACTH production is often so rapid that patients do not have time to develop classic Cushingoid physical exam findings, instead presenting with acute-onset hyperglycemia, pseudohyperaldosteronism, and generalized weakness. Prompt diagnosis and treatment are essential to improve outcomes.

Crinecerfont, a CRF1 Receptor Antagonist, Lowers Adrenal Androgens in Adolescents With Congenital Adrenal Hyperplasia.

Crinecerfont, a corticotropin-releasing factor type 1 receptor antagonist, has been shown to reduce elevated adrenal androgens and precursors in adults with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD), a rare autosomal recessive disorder characterized by cortisol deficiency and androgen excess due to elevated adrenocorticotropin. To evaluate the safety, tolerability, and efficacy of crinecerfont in adolescents with 21OHD CAH. This was an open-label, phase 2 study (NCT04045145) at 4 centers in the United States. Participants were males and females, 14 to 17 years of age, with classic 21OHD CAH. Crinecerfont was administered orally (50 mg twice daily) for 14 consecutive days with morning and evening meals. The main outcomes were change from baseline to day 14 in circulating concentrations of ACTH, 17-hydroxyprogesterone (17OHP), androstenedione, and testosterone. 8 participants (3 males, 5 females) were enrolled; median age was 15 years and 88% were Caucasian/White. After 14 days of crinecerfont, median percent reductions from baseline to day 14 were as follows: ACTH, -57%; 17OHP, -69%; and androstenedione, -58%. In female participants, 60% (3/5) had ≥50% reduction from baseline in testosterone. Adolescents with classic 21OHD CAH had substantial reductions in adrenal androgens and androgen precursors after 14 days of oral crinecerfont administration. These results are consistent with a study of crinecerfont in adults with classic 21OHD CAH.

Nelson's Syndrome: A Narrative Review.

Nelson's syndrome (NS) is an uncommon disease occurring as a complication of bilateral adrenalectomy (BLA) in patients with persistent Cushing's disease (CD) due to an adrenocorticotropin-producing pituitary tumor. The first reports of this syndrome were done in the 50s, although its pathophysiology is still not understood. Every year, between 1.8 and 2.6 cases are thought to occur per million people. It is characterized by hyperpigmentation, elevated adrenocorticotropic hormone (ACTH) plasma levels, and typical signs and symptoms related to pituitary adenomas, such as visual deficits due to optic pathway compression or decreased hormone production from the adenohypophysis. NS represents a challenge due to the lack of accepted diagnostic criteria and the complexity of its treatment. Moreover, the development of stereotactic radiosurgery (SRS) in the last few years has become an essential but controversial strategy for this syndrome. This review presents a comprehensive overview of NS.

Distinct serum steroid profiles between adrenal Cushing syndrome and Cushing disease.

Differentiating between adrenal Cushing syndrome (adrenal CS) and Cushing disease (CD) can be challenging if there are equivocal or falsely elevated adrenocorticotropic hormone (ACTH) values. We aim to investigate the diagnostic value of serum steroid profiles in differentiating adrenal CS from CD. A total of 11 serum steroids in adrenal CS (n=13) and CD (n=15) were analyzed by liquid chromatography with tandem mass spectrometry (LC-MS/MS). Age- and gender-specific steroid ratios were generated by dividing the actual steroid concentration by the upper limit of the relevant reference range. A principal component analysis (PCA) and an orthogonal partial least squares discriminant analysis (OPLS-DA) were performed. The PCA and OPLS-DA analyses showed distinct serum steroid profiles between adrenal CS and CD. Dehydroepiandrosterone sulfate (DHEA-S), dehydroepiandrosterone (DHEA), and androstenedione ratios were identified as biomarkers for discrimination by variable importance in projection (VIP) in combination with t-tests. The sensitivity and specificity of DHEA-S ratios<0.40 were 92.31% (95% CI 64.0%-99.8%) and 93.33% (95% CI 68.1%-99.8%), respectively, in identifying adrenal CS. The sensitivity and specificity of DHEA ratios<0.18 were 100% (95% CI 75.3%-100.0%) and 100% (95% CI 78.2%-100.0%), respectively, in identifying adrenal CS. Our data support the clinical use of the DHEA-S and DHEA ratios in the differential diagnosis of adrenal CS and CD, especially when falsely elevated ACTH is suspected.

Abstract #1413755: Subclinical Cushing’s Syndrome in an ACTH-secreting Pituitary Macroadenoma

Subclinical Cushing’s syndrome (SCS) is characterized by subtle cortisol hypersecretion, which does not result in the typical signs and symptoms of Cushing’s syndrome (CS). While many of the signs and symptoms of CS are common in the general population, there are some that are discriminatory and specific for CS: supraclavicular fat pads, proximal muscle weakness, facial plethora, and violaceous striae. SCS manifests mostly as obesity, type 2 diabetes, and hypertension. Diagnosing SCS is challenging; however, the best screening test to uncover the subtle hypercortisolism is the dexamethasone suppression test (DST). We report a case of SCS in a 62 years old Caucasian postmenopausal patient with a medical history of total thyroidectomy for Graves’ disease, post-surgical hypothyroidism, 7.4cm right pheochromocytoma status post partial right adrenalectomy, incidentally discovered pituitary macroadenoma (during imaging to look for subarachnoid hemorrhage), untreated type 2 diabetes mellitus (A1c 6.6% and stable for 1 year before treatment), hypertension, atrial fibrillation, cerebrovascular accident, and worsening migraines. Patient’s physical exam was mostly unremarkable; she had central obesity and bilateral lower extremity swelling. Pituitary work-up showed evidence of secondary hypogonadism and secondary hypothyroidism with elevated adrenocorticotropic hormone (ACTH) of 130 (AM range: 7.2-63) and cortisol of 12.6, at 11:52AM. Further work-up for hypercortisolism revealed non-suppressed cortisol (5.83mcg/dL) on the low dose DST and 49% suppression of cortisol and ACTH on the high dose DST. 24-hour urinary cortisol was normal. Patient did not perform the midnight salivary cortisol. Patient subsequently underwent trans-sphenoidal resection of the pituitary macroadenoma. Pathology analysis of the pituitary mass showed weak to moderate immunoreactivity for ACTH. Our patient had abnormal DST but normal 24hour urine cortisol. We may have missed her SCS if we screened her only with a 24hour urine cortisol. This confirms the fact that dexamethasone suppression test should be the first test in the evaluation of subclinical Cushing’s syndrome.