MON-079 A Case of Iatrogenic Cushing’s Syndrome Following Use of a Foreign Herbal Supplement

Disclosure: D. Bondarenko: None. M. Ahmad: None. G.A. McGrath: None. Background: Opioid suppression of the hypothalamic-pituitary-adrenal (HPA) axis via inhibition of corticotropin releasing hormone secretion leading to secondary adrenal insufficiency (AI) has been described in literature. Biochemical secondary AI is evident in 6-50% of patients on chronic opioids; fewer cases are reported presenting with clinical AI.1 We present a rare case of symptomatic opioid-induced AI (OIAI) with clinical improvement on initiation of hydrocortisone. Clinical Case: A 49-year-old female on daily buprenorphine (20 mg) and naltrexone (5 mg) presented to the hospital with syncope and hypotension (79/49 mmHg). AM cortisol was 6.2 mcg/dL, a cosyntropin stimulation test was performed, but there was technical difficulty with the results. She was started on midodrine 2.5 mg three times daily and referred to outpatient endocrinology for follow up. Weeks later, outpatient cosyntropin stimulation test showed baseline cortisol of 18 mcg/dL with increase to 26 mcg/dL. Simultaneous adrenocorticotrophic hormone (ACTH) was 16.9 pg/mL. AI was ruled out. Seven years later she presented with acute lethargy, confusion, and memory loss over several days. AM cortisol was 1.6 mcg/dL and cosyntropin stimulation test increased cortisol to 15.1 mcg/dL (normal response being 18 mcg/dL or greater). ACTH was 24 pg/mL. The abnormal cosyntropin stimulation test results are consistent with AI, and lack of elevation of morning ACTH is consistent with secondary AI.2 Hydrocortisone therapy was started and midodrine was held due to elevated blood pressure after initiation of steroids. She was discharged on hydrocortisone 15 mg each morning and 5 mg each afternoon. Within 10 days of initiation of glucocorticoid replacement therapy her neurologic symptoms improved and midodrine discontinued. Prescription Drug Monitoring Program (PDMP) review shows reduction of buprenorphine (16 mg) and naltrexone (4 mg). Conclusion: Data on management of OIAI and recovery of the HPA axis with or without cessation of opioid therapy is limited. This case highlights that opioids should be considered as a potential cause of secondary AI. Further follow-up of this case and other OIAI cases would provide insight into management of opioid therapy, continuation of glucocorticoid therapy, and recovery of HPA axis. This data could provide basis for OIAI management recommendations. Reference: (1) Fountas, A., Prof, S.V.U., Karavitaki, N. Opioid-induced endocrinopathies. Lancet Diabetes Endocrinol. 2020;8(1);68-80. (2) Bornstein, S.R., Allolio, B., Arlt, W., et al. Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline. J. Clin. Endocr. 2016;101(2);364-389. Presentation: Thursday, June 15, 2023

Disclosure: E. Shrestha: None. S.G. Albert: None. A. Ghimire: None. I. Iqbal: None. R.O. Akande: None. S. Portillo Canales: None.Advancements in immunoassays have improved the specificity of serum cortisol measurements compared to older assays. These newer assays allowed revisions of cutoff values for cortisol at 60 minutes for a normal cosyntropin stimulation test (CST), and thus rule out adrenal insufficiency (AI), from cortisol values of 18ug/dL to 14 ug/dL. Similarly, The Endocrine Society 2024 has used these newer assays to define values of AM cortisol which would predict a normal CST in individuals who were on long term corticosteroid therapy and therefore would eliminate the need for CST testing. However, AM cortisol cutoffs to predict a normal CST due to other presumed causes for AI needs reassessments. We aimed to compare morning cortisol levels with CST outcomes, using the newer generation assays cut off values to better predict normal CST responses in patients suspected of AI from various causes. We surveyed 100 patients who had CST between dates from 1/1/2024 - 6/30/2024 from the electronic health record of a midwestern community hospital system. Of the 95 patients, 51 were women, the mean age was 58.8 (SD ±17.8 years), 43 tests were performed as outpatient, 48 tests as inpatient and 4 in ICU settings. The pretest diagnoses were presumed adrenal abnormalities (n=10), hyponatremia (n=10), hypoglycemia (n=9), fatigue (n=19), hypotension (n=35), pituitary abnormality (n=7) and shock (n=4). Receiver operating curves (ROC) for an AM cortisol as a predictor of having a normal response at 60 minutes from a CST using the newer assay definition of a CST>14ug/dL was compared to previous criteria of a CST>18ug/dL. The newer CST assay criteria (>14 ug/dL) had a higher area under the curve (AUC 0.893) when compared to the previous definition of >18ug/dL (AUC = 0.777), p < 0.001. In these analyses, an AM cortisol level of 11.3 µg/dL with the newer assays was shown to preclude the need for CST testing, while with the older cut off criteria of >18ug/dL, an AM cortisol >15 µg/dL would have been required. A logistic regression analysis of the AM cortisol to predict a normal response of CST>14ug/dL showed that a baseline cortisol of 8.8ug/dL had a 95% positive predictive value (PPV). However, the PPV of having AI was less well defined because of the low prevalence of AI in this population. In conclusion, in this community hospital setting with low risk of AI (15%), a baseline AM cortisol between 8.8 µg/dL and 11.1 µg/dL can reliably preclude the need for further cosyntropin stimulation testing to predict a normal CST cortisol >14 µg/dL. The baseline cortisol was less able to predict AI. Further studies in higher risk patients need to be performed to confirm these observations.Presentation: Saturday, July 12, 2025

Disclosure: L. Vako: None. S. Kalik: None. N.E. Cusano: None. Background: Nivolumab is a Programmed Cell Death-1 (PD-1) immune checkpoint inhibitor used in cancer treatment. Nivolumab has been shown to cause endocrine-related adverse events, most commonly hypothyroidism, hypophysitis and adrenal insufficiency. Presentations can vary from vague symptoms to severe illness. Case Presentation: A 67-year-old man with bladder urothelial carcinoma was treated with a combination of gemcitabine, cisplatin, and nivolumab followed by nivolumab monotherapy. Prior to arrival in the emergency department, he had two episodes of new-onset absence seizures followed by a period of unresponsiveness while at an outpatient oncology appointment. These episodes resolved within a few minutes. Outpatient evaluation that morning showed: serum Na 124 mmol/L [reference range (RR): 135-145 mmol/L], AM cortisol 2.48 ug/dL (RR: 6.02-18.4 ug/dL), ACTH 17.4 pg/mL (RR: 7.2-63.3 pg/mL), TSH 9.93 uIU/mL (RR: 0.27-4.20 uIU/mL], and free T4 0.8 ng/dL (RR: 0.9-1.8 ng/dL). These results suggested new secondary adrenal insufficiency (AI) and primary hypothyroidism. He was hemodynamically stable. Admission evaluation showed: serum Na 128 mmol/L, serum osmolarity 265 mosm/kg (RR: 280-301 mosm/kg), urine osmolarity 111 mosm/kg (RR: 300-900 mosm/kg). He had reported drinking more water recently. He received one dose of hydrocortisone 100 mg IV for suspected AI and was placed on fluid restriction for suspected polydipsia. After four days, laboratories showed: AM cortisol 7.05 ug/dL, ACTH 15.9 pg/mL, TSH 6.52 uIU/mL, and free T4 0.624 ng/dL. He tested negative for thyroglobulin and thyroid peroxidase antibodies. There was otherwise normal anterior pituitary function of all other axes. CT scan of the head did not show any metastasis or acute processes. He did not undergo MRI as his symptoms improved rapidly. Na improved with one dose of steroid and fluid restriction. No further episodes of seizure-like activity occurred in the hospital. Additional steroids were held until the cosyntropin stimulation test was performed, demonstrating a baseline cortisol of 1.3 ug/dL with ACTH 10.4 pg/mL, and after 60 minutes, a suboptimal cortisol level of 11.3 ug/dL, confirming suspected secondary AI. He was started on hydrocortisone 10 mg in AM and 5 mg in PM. He was also started on levothyroxine 25 mcg for primary hypothyroidism. Na levels remained normal at 141 mmol/L after 1 month and he remained normotensive and seizure-free. Conclusion: This case highlights seizure as a severe presenting symptom of hyponatremia caused by Nivolumab-induced secondary AI and hypothyroidism. It is important to recognize adverse endocrine events related to check point inhibitors and initiate appropriate therapy. Presentation: Sunday, July 13, 2025

A 41year old female with a medical history significant for depression presented for evaluation of bilateral nipple discharge for 5 months. The patient reported that for the last 5 months she started noticing expressible nipple discharge. She reported no associated headaches, vision changes. She denied the use of vitamins, supplements, herbal remedies. No associated fatigue, changes in the shoe/ring size, heat/cold intolerance, tremors, recent weight changes. She denied neck enlargement, neck pain, dysphagia. The patient reported her menstrual cycles had always been heavy and irregular (every 33-50 days). She has never been pregnant. She has been on Sertraline for the last 4 years with no recent dose changes. Family history was significant for Birt-Hogg-Dubé (BHD) syndrome in father, brother, and sister. The patient has not been tested yet. Initial blood test revealed TSH 1.180 uiu/ml (0.45-4.5 uiu/ml), free T4 1.15 ng/dl (0.82- 1.77 ng/dl), T3 91ng/dl (71-180 ng/dl), FSH 3.8 mIU/ml, LH 3.7 mIU/ml, IGF-1 83 ng/ml (74-239 ng/ml), prolactin 107 ng/ml (4.79-23.3 ng/ml), monomeric prolactin 75.7 ng/ml, macroprolactin 23%, estradiol 16 pg/ml, AM Cortisol 6.5 ug/dl (6.2-19.4ug/dl). The urine pregnancy test was negative. Given low normal AM cortisol, a Cosyntropin stimulation test was done, which was normal. MRI Pituitary with contrast showed flattening of pituitary contour compatible with a partially empty sella turcica and an 8 mm fat intensity in hypothalamic region compatible with a lipoma, stable since last 4 years. The patient was referred to Neurosurgery for further evaluation. The patient remained asymptomatic and medical therapy was not indicated. Genetic testing for BHD was discussed. The patient will be followed in the clinic with a follow-up of prolactin levels and imaging as needed. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Introduction: Iatrogenic Cushing syndrome (ICS) can be caused by synthetic glucocorticoids administered through various routes. ICS caused by corticosteroid eye drops is an exceptional event, being more frequent in pediatric age. Herein, we describe a case of ICS associated with secondary adrenal insufficiency (SAI) caused by ocular topical corticosteroid treatment. Case Presentation: An 11-year-old girl was referred to our ocular inflammation department due to idiopathic, chronic, non-hypertensive, non-granulomatous bilateral anterior uveitis, treated with topical dexamethasone (eye drops, 1 mg/mL) for 1 year. During the past year, the child and her mother observed a gradual change in her physical appearance, particularly noting the development of a cushingoid facial appearance. Laboratory data revealed morning serum adrenocorticotropic hormone (ACTH) of 3.6 ng/L (7.2–63.3) and morning serum cortisol of 0.20 μg/dL (6.2–19.4). She was treated with methotrexate (15 mg/week, orally), and the topical corticosteroid regimen was progressively tapered and discontinued after 3 months. Nine months after the patient discontinued corticosteroid eye drops, her cushingoid face disappeared, and her laboratory data improved. Regarding the ophthalmological examination, the uveitis remained in remission with methotrexate, with no new episodes of intraocular inflammation. Conclusion: Although rare, ophthalmologists must be aware of ICS and SAI and prioritize using the least potent corticosteroid for the shortest duration necessary. Additionally, clinicians should avoid abrupt cessation of long-term corticosteroid therapy as this can precipitate an adrenal crisis in the presence of adrenal insufficiency. Introduction: Iatrogenic Cushing syndrome (ICS) can be caused by synthetic glucocorticoids administered through various routes. ICS caused by corticosteroid eye drops is an exceptional event, being more frequent in pediatric age. Herein, we describe a case of ICS associated with secondary adrenal insufficiency (SAI) caused by ocular topical corticosteroid treatment. Case Presentation: An 11-year-old girl was referred to our ocular inflammation department due to idiopathic, chronic, non-hypertensive, non-granulomatous bilateral anterior uveitis, treated with topical dexamethasone (eye drops, 1 mg/mL) for 1 year. During the past year, the child and her mother observed a gradual change in her physical appearance, particularly noting the development of a cushingoid facial appearance. Laboratory data revealed morning serum adrenocorticotropic hormone (ACTH) of 3.6 ng/L (7.2–63.3) and morning serum cortisol of 0.20 μg/dL (6.2–19.4). She was treated with methotrexate (15 mg/week, orally), and the topical corticosteroid regimen was progressively tapered and discontinued after 3 months. Nine months after the patient discontinued corticosteroid eye drops, her cushingoid face disappeared, and her laboratory data improved. Regarding the ophthalmological examination, the uveitis remained in remission with methotrexate, with no new episodes of intraocular inflammation. Conclusion: Although rare, ophthalmologists must be aware of ICS and SAI and prioritize using the least potent corticosteroid for the shortest duration necessary. Additionally, clinicians should avoid abrupt cessation of long-term corticosteroid therapy as this can precipitate an adrenal crisis in the presence of adrenal insufficiency.

Disclosure: D. Deyar: None. D. Nandiraju: None.Introduction: Hypercortisolism presents diagnostic challenges, particularly when assay interference complicates the evaluation of cortisol and ACTH (adrenocorticotropic hormone) levels. We present a case of a 78-year-old female with hypercortisolism and discordantly low ACTH levels, ultimately attributed to multifragment ACTH interference. This case underscores the importance of considering assay limitations in the diagnostic workup of endocrine disorders. Case Presentation: A 78-year-old female presented with generalized weakness, fatigue, nausea, vomiting and hypotension over two weeks. Six months prior, she was diagnosed with bullous pemphigoid and treated with a prednisone taper. Subsequent fatigue and weight loss led to evaluation for adrenal insufficiency, though cortisol remained elevated. Laboratory Findings: - K: 3.3 mmol/L (n 3.5-5.0) - Glucose 98 mg/dl (n 70-99) - AM cortisol: 49.5 µg/dL (n 5-25) - Cortrosyn stimulation test: Cortisol increased to 69.8 µg/dL - 1 mg dexamethasone suppression test: Cortisol 44.2 µg/dL (unsuppressed) - ACTH: <9 pg/mL (n 10-60)-Urinary free cortisol: 306-680 µg/24h (n 20-90) - DHEA-Sulfate: 17 µg/dL, (n 35-430) - FSH, LH, prolactin, TSH, free T4: Normal - Imaging studies were non-diagnostic. The patient’s lab findings suggested hypercortisolism, likely due to ectopic ACTH secretion. However, the ACTH assay revealed potential interference from multifragment ACTH, as the sample demonstrated non-linear dilution properties when used as a diluent for another ACTH-containing sample. This interference was attributed to unconnected ACTH fragments, which disrupted the sandwich immunoassay, leading to falsely low ACTH results. Clinical lesson: Assay interference can arise from various causes, including heterophilic antibodies, cross-reactivity with hormone fragments. The hypothesis of multi-fragment ACTH interference was supported by the discordance between clinical findings and biochemical results. Multi-fragment ACTH can arise from the degradation of ACTH precursors or post-translational modifications, leading to fragments that cross-react with certain assays but lack biological activity. This phenomenon can result in falsely low ACTH measurements. The patient’s clinical and biochemical findings are most consistent with ectopic Cushing’s syndrome, likely secondary to an occult malignancy. In this case, the interference was due to fragmented ACTH peptides. Multifragments form from improper POMC cleavage, degradation of pro-ACTH intermediates, or post-translational modifications in chronic inflammation (bullous pemphigoid) or malignancy. Discordant biochemical and clinical findings should raise suspicion for interference, and switching to mass spectrometry-based assays can help. Laboratory specialists can investigate heterophilic antibodies or hormone fragments.Presentation: Sunday, July 13, 2025

#1401368: Does A Male Sheehan’s Like Syndrome Exist?

Disclosure: N. Chamorro-Pareja: None. M.E. Manning: None. M.S. Haines: BioAge - Scientific Advisory Board. K.K. Miller: Amgen - Received study medication and investigator-initiated research grants, Bristol-Myers Squibb - Equity, General Electric - Equity, Boston Scientific - Equity, Becton Dickinson - Equity.Abiraterone, an androgen-production inhibitor, was FDA-approved in 2011 to treat metastatic prostate cancer. By inhibiting 17α-hydroxylase and C17,20-lyase, it also decreases cortisol production. Although prednisone 5-10 mg daily is routinely prescribed to prevent mineralocorticoid excess and concomitantly serves as glucocorticoid replacement therapy, adrenal insufficiency as a complication of this treatment may be under-recognized, resulting in underutilization of stress dose steroids during acute illness in this group of patients particularly prone to medical crises. Objective: To characterize the clinical presentation of patients receiving abiraterone who underwent cortisol testing and to evaluate the risk of adrenal insufficiency in this group. Methods: The Mass General Brigham Research Patient Database Registry was used to search patient medical records from January 1, 2014 to July 31, 2024. “Definite” adrenal insufficiency was defined as an outpatient AM serum cortisol <3 ug/dL (before 10AM) or a peak serum cortisol <15 ug/dL on a cosyntropin stimulation test (CST). Probable adrenal insufficiency was defined as an inpatient AM serum cortisol <3 µg/dL or outpatient AM serum cortisol 3-5 µg/dL. The medical records of these patients, including provider encounters, laboratory results, and medication records were reviewed. Results: Out of >4000 patients who received abiraterone, only 171 (4%) underwent cortisol testing of any kind. Among these, 23 (13%) met criteria for adrenal insufficiency, and 14 (8%) met the criteria for probable adrenal insufficiency. In patients with definite adrenal insufficiency, median age was 74 years (IQR 70-82), and 87% were White. Testing was prompted by symptoms in 83% of patients, with the most common being fatigue (57%), anorexia/weight loss (35%), and orthostatic hypotension/dizziness (39%). The median AM cortisol was 2.5 µg/dL (IQR 0.8-3.9) and the median peak cortisol on CST was 5.1 µg/dL (IQR 2.6-9.1). Forty-three percent (n=10) received stress dose steroids or sick day dosing after diagnosis of adrenal insufficiency. Conclusion: Despite the known effect of abiraterone on cortisol synthesis, fewer than 5% of patients treated with this medication underwent cortisol testing, yet nearly 15% of those tested met criteria for adrenal insufficiency. The true incidence of adrenal insufficiency in this population remains uncertain. However, our findings underscore the importance of maintaining a high clinical suspicion for adrenal insufficiency in patients on abiraterone. Educating patients about this complication and ensuring timely administration of stress dose steroids during acute illness are critical. Further studies are warranted to clarify the incidence and optimal management strategies for adrenal insufficiency in this setting.Presentation: Monday, July 14, 2025

Disclosure: M.D. Lundholm: None. M. Ortega Abad: None. P.P. Rao: None.Introduction: Adrenal insufficiency (AI) is a life-threatening condition requiring timely identification and management. The 3-point cosyntropin stimulation test (CST) is used to assess for AI, yet is challenging to coordinate: a basal cortisol blood draw is followed by intravenous or intramuscular 250 mcg of cosyntropin (synthetic ACTH) with subsequent cortisol blood draws at 30 and 60 minutes. We aim to analyze our system’s adherence to the inpatient CST procedure to ensure the accurate and timely diagnosis of AI. Methods: This retrospective quality and patient safety project includes all adult patients who had an inpatient CST performed between September 2020 - February 2022 across the Northeastern Ohio region of our healthcare system. Charts were reviewed for cross-reacting steroid use (prednisone, methylprednisolone, hydrocortisone), albumin level, and adherence to the CST procedure. Results: We include 514 patients, mean age 60.4 ± 15.7 years, 53.5% (N=275) female, who collectively had 554 inpatient CSTs, of which 14.4% (N=80) were consistent with AI. Procedural issues were identified in 30.1% (N=167) of all CSTs: 20.0% (N=111) had blood draw collection or timing issues, 6.1% (N=34) ACTH was not given, or given after the test ended, 4.3% (N=24) were on cross-reacting steroids, and 2.3% (N=13) had lab errors. Additionally, 18.2% (N=101) tests were performed in the setting of albumin <2.5 g/dL, only 5.0% (N=5/101) checked free cortisol levels, yet 85.1% (N=86/101) reached cortisol ≥12.6 mg/dL to exclude AI. Procedural issues or low albumin interfered with 44.2% (N=245) of all tests. Of those results consistent with AI, 57.5% (N=46/80) were performed incorrectly or with low albumin without free cortisol, potentially over-diagnosing AI. Of those results ruling out AI, 2.5% (N=12/474) had cross-reacting steroid interference risking a missed diagnosis of AI. In all, 10.4% (N=58) of tests were unable to diagnose or rule out AI. Endocrinology was consulted in 30.5% (N=169) of CSTs with a trend toward higher consult use in cases with procedural issues or low albumin (50.3% vs 41.6%, p=0.057). Discussion: At a large academic institution, over 30% of inpatient CSTs were performed incorrectly, most often due to blood draw timing issues, omitted cosyntropin, and interfering steroid use. Low albumin remains a challenge and free cortisol is rarely used in part due to long turnaround time. Despite this, the majority of patients with low albumin were still able to exclude AI with total serum cortisol. Overall,10.4% of CST results were uninterpretable, which can delay a critical diagnosis of AI, or cause over-diagnosis of AI. Given the importance of prompt steroid intervention, but also the harms of unnecessary steroid use, we must prioritize performing the CST correctly the first time. Further study is planned to determine the impact of education and safety interventions to address these issues.Presentation: Sunday, July 13, 2025

#1406235: Silent Corticotroph Adenomas are More Aggressive than Other Nonfunctional Pituitary Adenomas

IntroductionAdrenal insufficiency (AI) has been reported due to the use of budesonide and itraconazole. We report an unusual presentation of adrenal insufficiency from the use of triamcinolone and itraconazole.Clinical Case46-year-old man with a history of NASH and alcoholic cirrhosis requiring liver transplant presented to ER with two weeks of progressive lower extremity weakness. He reported difficulty climbing stairs and getting up from a chair. He denied anorexia, nausea, vomiting, abdominal pain, or lightheadedness. He was treated with itraconazole for diffuse histoplasmosis for over one year and received one dose of intra-articular triamcinolone 40mg for shoulder pain 2 weeks prior to the hospital admission. Physical exam was significant for proximal weakness, ecchymoses on upper and lower bilateral extremities, mild truncal obesity, but no violaceous striae, moon facies, dorsocervical fat pad or supraclavicular fullness. Laboratory evaluation was notable for sodium 129 mEq/L (n: 135-145), potassium 5.9 mEq/dl (n: 3.5-5), albumin 2.9 g/dl (n: 3.5-5) and glucose 345 mg/dl (n: 70-140), ACTH of 6 pg/ml (6-20) AM cortisol of <1 ug/dl (n: 4-20), aldosterone <1 ng/dl (n: 3-16), and plasma renin activity (PRA)20.54 ng/mL/h (n: 0.25-5.82). Serum cortisol increased to 3.4 ug/dl at 60 minutes of cosyntropin stimulation test, consistent with adrenal insufficiency. Synthetic glucocorticoid panel detected triamcinolone. Patient was discharged on hydrocortisone and fludrocortisone with marked clinical improvement. Abdominal MRI 3 months after admission did not show any adrenal involvement by histoplasmosis. Fludrocortisone was slowly titrated off and only hydrocortisone continued. Repeat evaluation 6 months after last triamcinolone injection demonstrated recovery of HPA axis with peak cosyntropin stimulation cortisol level 16.3 ug/dL (assay by Abbott Alinity) and recovery of renin/angiotensin/aldosterone axis (AM aldosterone 7 ng/dl, renin 2 ng/ml/h). Repeat synthetic glucocorticoid testing confirmed clearance of triamcinolone.ConclusionItraconazole is CYP3A inhibitor that has been shown to decrease the metabolism and clearance of different corticosteroids. While our patient's lab results supported a diagnosis of AI, it was unclear if the etiology was primary (PAI) or central AI (CAI). The Na+, K+, aldosterone and PRA levels support a diagnosis of PAI; whereas the suppressed ACTH level supports CAI. We believe that our patient had an atypical presentation of both PAI due to histoplasmosis and CAI due to itraconazole/triamcinolone. This confounding picture can potentially be explained by an underlying PAI that may have been masked and exacerbated by the HPA axis suppression of the itraconazole/triamcinolone combination.Presentation: No date and time listed

The Neuroendocrine Effects of Traumatic Brain Injury

Neuroendocrine dysfunction after traumatic brain injury (TBI) is under-diagnosed, under-treated, and may adversely affect the rate of recovery. Single or multiple pituitary-target hormone disruption occurs in up to two-thirds of persons with TBI, most commonly affecting the gonadal and growth hormone axes. The time course of decline in and recovery of pituitary function in relation to cognitive dysfunction and rehabilitation progress are not well described. This article reviews the clinical spectrum of neuroendocrine deficits after TBI and their underlying mechanisms. Future studies of the effects of hormonal replacement on recovery are recommended.

Introduction: Megestrol acetate (MA) is a synthetic progestin that is often prescribed for anorexic patients with HIV due to its effects on weight gain and appetite stimulation. It can cause several endocrine/metabolic abnormalities. Chronic use of MA can cause exogenous Cushing’s Syndrome (ECS) and iatrogenic adrenal insufficiency (AI) due to its stronger affinity for the glucocorticoid receptor (GR). It can also cause gonadotropin suppression, diabetes and hyperprolactinemia. We present a case of a young woman with perinatal HIV/AIDS that developed ECS secondary to MA treatment in the setting of fatigue, rapid weight gain and irregular menses. Case: A 19 year old female with perinatal HIV/AIDS (CD4<200) was treated with MA (200mg/day for 5 months) for anorexia and weight loss. On exam she was pre-hypertensive (BP 138/62), obese (BMI 43.07, SDS +2.25; weight 114kg, SDS +2.34) with increased fat deposition over upper back and abdominal striae, excessive weight gain (21.5 kg in 5 months) suggestive of ECS. She had menarche at 13 years of age and had regular menses until starting MA, upon which she developed oligomenorrhea. A random serum cortisol level was <0.5ug/dl at 1pm with a low ACTH <1.5pg/ml and DHEAS of 13.4ug/dl. Her FSH was 3.4 mIU/L and LH 0.82 mIU/L, estradiol was <2pg/dl and total testosterone <2.5ng/dl consistent with secondary hypogonadism. Liver/kidney function, prolactin and lipid profile were normal. HbA1c increased from 5.3 to 6.4% in 8 months so she was started on metformin. ECS with AI, central hypogonadism and diabetes were all attributed to MA therapy. MA was discontinued gradually over two weeks. Stress dosing of glucocorticoids were advised as needed. Results: Gradual recovery of HPA axis was noted after discontinuation of MA. Two months after taper, serum ACTH level rose to 2.5pg/ml but AM cortisol level remained low at <0.5ug.dl. Her HPA axis showed partial recovery by 5 months with ACTH level of 53.2pg/ml and AM cortisol level of 5.5ug/dl. By 8 months after discontinuing MA therapy, AM cortisol was 9.3ug/dl, suggesting complete HPA axis recovery. Her HPG axis also normalized by 8 months with FSH 6.6 mIU/L and LH of 14.6 mIU/L, estradiol 32pg/dl with regular menses. Metformin was discontinued at 4 months due to hypoglycemia and HbA1C of 5.7%. Subsequently, euglycemia was achieved (HbA1C of 5.4%) within 9 months. BMI was stable (BMI 43.07, SDS +2.25; weight 114kg, SDS +2.34). Conclusion: Multiple endocrine abnormalities may occur due to MA therapy due to its affinity to bind with glucocorticoid and progesterone/androgen receptors. ECS and AI are known to occur with various forms of glucocorticoid use, but rarely can be seen with MA therapy. HPA axis, HPG axis and metabolic parameters should be evaluated and monitored carefully during MA therapy.

What Predicts Adrenal Insufficiency in Patients with Thalassemia Major?