Rare Disorder Research Articles

6369 Weiss-Kruszka Syndrome and Growth Hormone Deficiency, Adrenal Insufficiency, and Morbid Obesity

Abstract Disclosure: T. Falcon-Rodriguez: None. N. Solano: None. A. Diaz: None. Background: Weiss-Kruszka syndrome (WKSA) is a rare autosomal dominant genetic disorder caused by heterozygous loss-of-function variants in the ZNF462 gene. Individuals affected by this condition exhibit distinctive craniofacial features, ptosis, dysgenesis of the corpus callosum, hearing loss, intellectual disability, and hypotonia. There is one other case report that described a boy with empty sella syndrome with growth hormone deficiency and delayed puberty. Case Presentation: We present the case of a 15-year-old boy who initially came under the care of endocrinology at age 9 due to severe obesity and short stature. Past medical history included ADHD (for which he was on stimulants since age 5), microcephaly, VUR, asthma, and developmental delay. He grew along the 2nd percentile for height from the ages of 6 and 13, after which his growth velocity notably decelerated. His initial bone age at 9 years old was advanced by 3 years. His BMI had exceeded the 99th percentile since age 3. His family history was relevant for maternal type 1 diabetes mellitus, paternal height of 165 cm, and maternal height of 160 cm. Upon physical examination, notable findings included short stature, severe obesity, a low anterior hairline, arched eyebrows, upslanted palpebral fissures, low-set ears, a tubular and short nasal bridge, and an exaggerated cupid's bow. At age 9, the patient was diagnosed with growth hormone (GH) deficiency following a clonidine and glucagon stimulation test, with a GH peak of 1.9 ng/mL (normal >7 ng/mL). Additionally, he was diagnosed with adrenal insufficiency (cortisol peak of 5 ug/dL, after 250 mcg of cosyntropin). A brain/sella MRI revealed a hypoplastic pituitary gland. Subsequently, hydrocortisone replacement was initiated at a dose of 6 mg/m2/day, and GH treatment at a weekly dose of 0.3 mg/kg. Despite treatment with growth hormone and IGF-1 levels on the upper side of the normal range, his growth velocity did not improve significantly. He reached his peak adult height of 150 cm at age 15. His BMI had consistently been at the 99th percentile. According to his mother, he did not have issues with satiety, and his portion sizes were considered normal. He did not consume fast foods or sugary drinks, and his level of physical activity was suboptimal. Whole Exome Sequencing identified a heterozygous de novo pathogenic variant in the ZNF462 gene, specificallyc.2664 C>A, p.(C888*) (NM_021224.4), consistent with the diagnosis of Weiss-Kruszka syndrome (OMIM # 618619). Conclusion: We present, to our knowledge, the first report of morbid obesity and central adrenal insufficiency in a child with WSKA. GH deficiency had been previously reported in 1 patient with WSKA. The finding of a hypoplastic pituitary gland supports the diagnosis of GH deficiency and central adrenal insufficiency. Presentation: 6/3/2024

7443 Severe Hypothyroidism and Adrenal Insufficiency in a 27-Year-Old Male with Klippel-Feil Syndrome: A Case Report

Abstract Disclosure: S. Almardini: None. F. Haddadin: None. L. Aoun: None. F. Saliba: None. J. Zaidan: None. Background: Klippel-Feil syndrome (KFS) is a rare congenital disorder characterized by improper segmentation of the cervical vertebrae. The classical clinical triad consists of short neck, low posterior hairline, and limited neck mobility. It is uncommonly associated with endocrine abnormalities. We present a rare case of KFS with severe primary hypothyroidism. Case Presentation: A 27-year-old male with KFS presented for evaluation of profound fatigue and lack of energy. His vital signs revealed a heart rate of 50 and a borderline low blood pressure. On physical exam patient was noted to be lethargic and icteric, thyroid exam was limited due to patient short neck. Labs were consistent with severe hypothyroidism TSH of 825 mIU/L, total T4 <0.4 mcg/dL, low 8 AM cortisol of 4.3 mcg/dL, elevated LDL at 333 mg/dL, elevated liver enzymes AST 491 U/L, ALT 294 U/L, neutropenia with WBC 2.69 x10^3/uL 20% neutrophils and anemia Hb 12 g/dL. TPO and thyroglobulin antibodies were positive at 149.0 and 109.0 IU/mL respectively, 21 hydroxylase antibodies were negative. Thyroid Ultrasound showed small and diffusely heterogenous thyroid. Patient was started on Levothyroxine 125 mcg daily and hydrocortisone with improvement in his symptoms as well as normalization of his lipid panel, liver enzymes and neutropenia. The patient was continued on levothyroxine 125 mcg, hydrocortisone was tapered and repeat cortisol levels were normal. Discussion: This case demonstrates an unusual association between KFS and hypothyroidism secondary to Hashimoto thyroiditis, likely representing an incidental finding rather than a causative relationship. The cervical spinal abnormalities and short neck characteristic of KFS could potentially lead to compression of neurological and vascular structures in the neck. However, this is unlikely to fully explain our patient's hypothyroidism. There are few published case reports of KFS with endocrine disorders in the literature that describe incidental findings like autoimmune thyroiditis and hypoparathyroidism, but there is no known biological mechanism linking KFS and endocrine dysfunction. Moreover, there is no evidence in either our patient's case or in existing literature to suggest a higher occurrence of autoimmune disorders like Hashimoto in such individuals. Conclusion: we present a novel case of KFS found incidentally with primary hypothyroidism. While these endocrine disorders could compound the growth delay and developmental issues typically seen in KFS, they do not appear to be causally related. This case highlights the need to monitor endocrine function in KFS patients and serves as a reminder that common conditions may co-occur simply by chance. Presentation: 6/3/2024

7984 A Challenging Case Of Hyperphosphatemic Familial Tumoral Calcinosis

Abstract Disclosure: T.G. de Souza: None. T.J. Weber: None. Introduction: Hyperphosphatemic Familial Tumoral Calcinosis (hFTC) is a rare, autosomal recessive metabolic disorder characterized by elevated serum phosphate levels and the accumulation of calcium phosphate deposits in soft tissues. There are fewer that 150 genetically confirmed cases in the literature. There are no consensus guidelines; therapeutic approaches are guided by case reports or series. This case serves to heighten awareness of therapeutic strategies including global health considerations for the disabled adult with a rare bone disorder. Case: A 32-year-old African-American woman presented to establish care for hFTC, for which she takes ibuprofen for disabling bilateral hip pain. hFTC was diagnosed in early childhood and managed at a large children’s hospital. Therapeutic modalities relied on operative resection of skin lesions on eruption. She describes cosanguinous parentage, consignment to foster care as a child and homelessness as an adult. She has not had adult endocrine care for her hFTC. Her medical comorbidities include major depressive disorder, PTSD and suicide attempt. She reports one uncle with hFTC noting that his phenotype was not significantly disabling and apparent recession of his lesions with age. Her parents did not have symptoms of hFTC. Radiographically, she had amorphous calcium deposits over both hips (her primary sites of severe pain), upper back (site of painless spontaneous eruptions), and left elbow without pain or skin penetration, as well as hyperostosis of the ilium bilaterally. She noticed waxing and waning of her eruptions with her menstrual cycle, such that lesions worsen in the luteal phase. Megestrol acetate also induced new eruptions. Examination shows brown staining to all teeth with several missing teeth. She had a marked lower extremity limb length discrepancy with severe restriction of hip abduction. Blood chemistries were grossly normal, including renal function, calcium, uric acid and PTH. Serum phosphorous was elevated at 5.2 (2.3 - 4.5 mg/dL). CT showed bilateral nephrocalcinosis. We instituted treatment with a low phosphorous diet, sevelamer to reduce intestinal phosphate absorption and acetazolamide to increase urinary phosphate excretion. For her pain and functional disability, we recommended continued NSAIDs, physical therapy and social work consultation to facilitate continued access to care. Conclusions: This case uniquely describes hFTC symptom fluctuation with the menstrual cycle, worsening with increased progesterone, suggesting a possible role of gonadal hormones on FGF-23 biology. It also highlights the socioeconomic burdens that can accompany rare bone disease, which become more pronounced as the patient achieves adulthood. Successful transition of care from pediatric to adult endocrinologist, in addition to engaging multi-disciplinary support, is essential in optimizing life-long care in hFTC. Presentation: 6/1/2024

7293 An Unusual Case Of Adult-Onset Heterozygous HHRH In A Male With Normal Phosphorus And Severe Osteoporosis

Abstract Disclosure: M. El Najjar: None. A. Sabet: None. D. Willard: None. Introduction: Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a rare genetic disorder characterized by renal phosphate wasting, which can affect bone metabolism. Although onset is typically in childhood, adult-onset forms have been described, and the manifestation depends on the zygosity of each patient. Most commonly, adults with HHRH demonstrate markedly reduced bone density and multiple fractures. Heterozygotes have milder presentations with mild hypophosphatemia, hypercalciuria, and nephrolithiasis, usually without bone disease; however, it is less well characterized. Case report: A 73-year-old man suffered an L1 vertebral compression fracture while playing golf. Bone mineral density testing revealed T-scores of -0.9 at the lumbar spine and -3.4 at the femoral neck (Z-score -2.6). He started alendronate 70 mg weekly for osteoporosis treatment. A year later, the patient sustained an L3 vertebral compression fracture while on treatment with no improvement in his bone density. His family history was remarkable for osteoporosis in his mother but no nephrolithiasis or hypercalcemia. Physical examination was unremarkable. Laboratory evaluation was notable for a 1,25-dihydroxyvitamin D of 87 pg/mL (18-72 pg/mL) , a 24-hour urine calcium of 240 mg/g Cr (30-210 mg/g),a serum PTH of 9 pg/mL (16-77 pg/ml) , but otherwise a normal serum calcium level of 9.4 mg/dL (8.6-10.3 mg/dL) and serum phosphate level of 2.2 mg/dl (2.1-4.3 mg/dl). Genetic testing revealed heterozygosity for SLC34A3 mutation, which is associated with HHRH. The patient discontinued alendronate and started 250 mg phosphorus supplementation 4 times daily. At 6 months follow up, he reported improvement in his body aches, and biochemical testing showed normalization of his 24-hour urine calcium to 171 mg/g Cr and serum PTH to 21 pg/mL. Repeat bone density scan after 1 year of phosphorus supplementation showed T-scores of -0.3 at the lumbar spine (5.8% increase) and -2.6 at the femoral neck (15.5% increase). Clinical Lesson: HHRH is an autosomal recessive hypophosphatemic rickets associated with mutations of the SLC34A3 sodium-phosphate cotransporter, where it is believed that selective phosphate wasting leads to increased calcitriol, in contrast to other forms of hypophosphatemic rickets, causing increased intestinal calcium absorption and resulting hypercalciuria. Adult-onset forms of HHRH have been described in heterozygous carriers of the SLC34A3 mutation and usually present with low to low-normal phosphate levels, hypercalciuria, and nephrolithiasis but without bone disease. However, clinical variations of heterozygous carriers have also been recognized, and therefore are likely underdiagnosed. Our patient’s serum phosphorus level was within the normal range, and hypophosphatemic rickets could have been missed if a more extensive laboratory evaluation had not been performed. Presentation: 6/1/2024

7655 Genetic Mysteries Unveiled: Unusual Mutation Unraveled In Hypophosphatasia

Abstract Disclosure: A. Sharma: None. P. Katikaneni: None. S. Tanveer: None. K. Selk: None. Introduction: Hypophosphatasia (HPP), an inherited dental-osseous metabolic illness, is caused by inactivating mutations in the gene encoding the tissue-nonspecific isoenzyme of alkaline phosphatase (TNSALP), which leads to a decrease in TNSALP enzymatic activity. Patients with HPP typically experience dental and skeletal mineralization issues as their most common symptoms; musculoskeletal abnormalities, numerous fractures, tiredness, and migraines are less common clinical presentations. Case Report: Our 75-year-old male patient initially presented 1.5 years prior following a spontaneous T12 vertebral fracture. A bone biopsy was performed and did not reveal evidence of malignancy. Testing for SPEP/UPEP was not consistent with myeloma, and thyroid testing was also unrevealing. His alkaline phosphatase level was consistently <40 IU/L since 1999. An evaluation was done for low alkaline phosphatase and secondary reasons for bone loss. This testing did not reveal vitamin D deficiency, parathyroid disease, hypophosphatemia, laboratory evidence of celiac disease, hypogonadism, or hypomagnesemia. A vitamin b6 level was markedly elevated at 119 ng/mL (ref range 2.1-21.7) while not on supplementation. He had noticed multiple fractures as a child, but he had written them off as minor injuries. He could clearly remember breaking his right wrist and clavicle. As an adult, he had rib fractures and a foot fracture. He was unable to recollect losing his primary teeth. Almost all his teeth are crowns or implants despite taking exceptional care of them. He did not have joint hypermobility. Genetic testing revealed the patient was heterozygous for an ALPL gene variant, c.876_882delinsT. It was a variant of undetermined significance at that time. His daughter also was found to have a low alkaline phosphatase and the same genetic test result. She also has experienced dental carries and joint pain. Our patient initiated teriparatide due to the need for more urgent therapy for extensive spinal surgery. He was later transitioned to asfotase alfa therapy and has not had any further fractures at the time of this report. Discussion: Hypophosphatasia is a rare inborn disorder due to mutations in the tissue nonspecific alkaline phosphatase gene ALPL and is characterized by low ALP levels. Affected individuals will also have elevated vitamin b6 levels and urinary phosphoethanolamine (PEA) levels. Early diagnosis of HPP is necessary to prevent bone fracture pain and improve quality of life. Inaccurate assessments can miss diagnoses of parents and other family members and even lead to lost opportunities to treat a patient with a substantial illness burden. This case highlights the mutation c.876_882delinsT as a likely pathologic variant in the ALPL gene. It also supports that patients with HPP can also respond to teriparatide treatment. Presentation: 6/2/2024

8131 A Rare Case of Autoimmune Polyendocrine Syndrome; a Menopause Despite Replacement Therapy

Abstract Disclosure: M.E. Chacon Cruz: None. M. Sanchez Cordero: None. R.M. Roman Torres: None. G. Guerra Velazquez: None. Polyendocrinopathy is a heterogeneous group of disorders leading to dysfunction of multiple endocrine glands and other tissues. The syndromes can occur in patients from early infancy to old age and new components of a given syndrome can appear throughout life. APS can be classified into APS type 1 and APS2-4. APS-1 is a rare monogenic autosomal recessive autoimmune disorder consisting of the triad of chronic mucocutaneous candidiasis, hypoparathyroidism and adrenal insufficiency. APS2 require presence of Addison disease, autoimmune thyroid disorder and type 1 diabetes. APS 3 requires presence of Thyroid autoimmune disease associated with other autoimmune diseases. APS4 is a combination of organ specific autoimmune disease non included in a previous group. Autoimmune oophoritis is found in approximately 4 percent of females who presented with spontaneous primary ovarian insufficiency and may occur in type I and II syndromes of polyglandular autoimmune failure. This is the case of 44 year old female patient with history of hypertension, hypoparathyroidism diagnose at the age of 9 year old, vitiligo and premature ovarian failure diagnose at the age of 16 year old. Patient reported that started with multiple episodes of watery non bloody diarrhea and arthralgia. Patient went to her Pediatrician and they found hypocalcemia hyperphospathemia. Patient mineral was replaced with medication and then followed by pediatric endocrinologist. Patient continues with normal life, but menstrual periods had not started even at age 16th. Laboratory work up was done and premature ovarian failure was diagnosed after that, patient started with progesterone and estrogen to induce menstrual periods. Menstrual periods began regularly and monthly. Patient continues taking medication regularly, phoslo, calcitriol, progestin and estradiol without problem until this year that despite regular medication, started with signs and symptoms of menopause with irregular menstrual periods, palpitations hot flashes, sweating, anxiety and sleep problems. Patient met criteria for APS4 due to combination of organ specific autoimmune disease such premature ovarian failure, vitiligo and hypoparathryroidism. This case is extremely important since despite the fact that there is no family history of either endocrinological or autoimmune diseases, our patient debuts throughout her life with several autoimmune diseases, such as premature ovarian failure and vitiligo. Patient had Schedule appointment with gynecologist who increased the dose of progestin and estradiol. This case highlights the importance of being vigilant about new components of a syndrome developing at different times though a patient's life. As described, autoimmune diseases commonly are related to other diseases, but without a good clinical history and physical examination could be misdiagnosed affecting the quality of life of those patients. Presentation: 6/2/2024

Abetalipoproteinemia with angioid streaks, choroidal neovascularization, atrophy, and extracellular deposits revealed by multimodal retinal imaging

ABSTRACT Purpose Abetalipoproteinemia (ABL, MIM 200,100) is a rare autosomal recessive disorder caused by nonfunctional microsomal triglyceride transfer protein leading to absence of apolipoprotein B-containing lipoproteins in plasma and a retinitis pigmentosa-like fundus. The MTTP gene is expressed in retinal pigment epithelium (RPE) and ganglion cells of the human retina. Understanding ABL pathophysiology would benefit from new cellular-level clinical imaging of affected retinas. Methods We report multimodal retinal imaging in two patients with ABL. Case 1 (67-year-old woman) exhibited a bilateral decline of vision due to choroidal neovascularization (CNV) associated with angioid streaks and calcified Bruch membrane. Optical coherence tomography were consistent with basal laminar deposits and subretinal drusenoid deposits (SDD). Results Case 2 (46-year-old woman) exhibited unusual hyperpigmentation at the right fovea with count-fingers vision and a relatively unremarkable left fundus with 20/30 vision. The left eye exhibited the presence of nodular drusen and SDD and the absence of macular xanthophyll pigments. Conclusion We propose that mutated MTTP within the retina may contribute to ABL retinopathy in addition to systemic deficiencies of fat-soluble vitamins. This concept is supported by a new mouse model with RPE-specific MTTP deficiency and a retinal degeneration phenotype. The observed range of human pathology, including angioid streaks, underscores the need for continued monitoring in adulthood, especially for CNV, a treatable condition.

6821 Characterization Of A Novel Oral Small Molecule PTH1R Agonist: Proof Of Concept For An Alternative To Injectable Peptide-Based Therapy For Hypoparathyroidism

Abstract Disclosure: J. Zhang: None. I. Gomez: None. C. He: None. J. Wang: None. X. Du: None. K. Nguyen: None. K. Alvarez: None. A.M. Mirza: None. Hypoparathyroidism (HP), a rare endocrine disorder characterized by insufficient levels of parathyroid hormone (PTH), leads to hypocalcemia and hyperphosphatemia. Most HP cases arise due to damage of the parathyroid glands during thyroid or neck surgery. HP symptoms include severe muscle cramps, tingling, burning and numbness, memory loss, and headaches, all leading to a decreased quality of life. Calcium and vitamin D supplementation do not fully ameliorate the disease and may contribute to renal disease. Chronic HP increases the risk of major complications, such as calcium depositions in the brain, eye, and kidneys. Similarly, it can lead to low bone turnover and increased bone mineral density with associated increased bone mineralization. In comparison to standard of care and traditional injectable peptide-based therapies, oral small molecules may have multiple advantages clinically. However, there are no oral small molecules currently in development. PTH functions through activation of the parathyroid hormone 1 receptor (PTH1R), a class B G protein-coupled receptor. The main target tissues for PTH1R activation include bone and kidney. In the kidney, PTH increases tubular reabsorption of calcium and promotes renal excretion of phosphate. In bone, PTH stimulates bone turnover and mobilizes calcium into the circulation to maintain serum calcium. Here we describe the characterization of SP-1462, a novel, potent, and selective oral small molecule, and show that, like the PTH peptides, it acts on PTH1R as an agonist and elicits similar downstream functions in vitro and in vivo. To assess PTH1R engagement in the major targeted organs, kidney and bone, primary human renal proximal epithelial cells (RPTEC) and a human osteoblast cell line (Saos-2) were used, respectively. RPTECs treated with PTH and SP-1462 showed significant changes in transporter genes (SLC22A2 and SLC13A1), immune related genes (CCL2 & DPP4), and matrix reorganization genes (ITGA5 and COL1A1). Saos-2 cells treated with PTH and SP-1462 both significantly affected the expression of Wnt signaling genes (DKK1 and TCF7) and the expression of coupling genes that bridge anabolic/catabolic activities (M-CSF, RANKL, HDAC4, and OPG). Importantly, oral administration of a single dose of SP-1805 in a rat surgical thyroparathyroidectomy (TPTx) model resulted in significant upregulation of serum calcium levels for a period of 24 hours in a dose dependent manner at 3, 10 and 30 mg/kg. The window of calcium upregulation is comparable to injectable PTH peptides currently in development to treat hypoparathyroidism. These data suggest that oral small molecule PTH1R agonists engage PTH pathways similar to native PTH and have the potential to replace injectable PTH peptides to treat PTH-related disorders, including hypoparathyroidism. Presentation: 6/3/2024

5118 When Thyroid Gland Is Not Made Of Thyroid Cells

Abstract Disclosure: A. Bulut: None. L. Ma: None. J.P. Noordzij: None. S.Y. Lee: None. Introduction: Neurofibroma is a type of peripheral nerve tumor that can arise sporadically or be a part of neurofibromatosis type 1 (NF1), a rare genetic disorder. Neurofibromas within the thyroid gland are extremely rare. Here, we present the fifth reported case of primary neurofibroma of thyroid gland. Case: A 60-year-old woman with history of systemic lupus erythematosus and hypertension presented with enlargement of left thyroid gland. She was diagnosed with Graves’ disease 40 years ago, which was treated with right thyroid lobectomy one year after the initial diagnosis. Five years after the surgery, she had recurrence of her symptoms and received radioactive iodine ablation with subsequent hypothyroidism. On presentation to endocrine clinic, she had thyroid ultrasound (US), which showed surgically absent right thyroid lobe and enlarged heterogenous left thyroid lobe measuring 5.1 cm x 3.8 cm x 3.9 cm with scant blood flow without discrete nodules. In interim, patient developed dysphagia and globus sensation. Repeat thyroid US showed enlargement of left lobe to 5.6 cm x 3.7 cm x 4.7 cm. Patient underwent completion thyroidectomy. Surgical pathology showed neurofibroma (S-100+, CD34+ and MSA-) without any thyroid parenchyma. Whole-body scan revealed no other evidence of tumors. Patient was referred for genetic analysis. Discussion: Neurofibromas are benign peripheral nerve system tumors primarily consist of Schwann cells along with other components of perineurium. They can occur as a sporadic lesion which accounts for 90% of solitary neurofibroma cases or be a part of NF1 on rare occasions. NF1 is an autosomal dominant genetic disorder due to germline mutation in NF1 gene located on chromosome 17q11.2, whose manifestations include café-au-lait macules, Lisch nodules, skeletal abnormalities, neurological deficits, and other benign and malignant tumors. Neurofibromas are the hallmarks of NF1. There are only few cases in the literature reported neurofibromas adjacent to or originating from thyroid gland. To the best of our knowledge, there have been only four other cases reporting primary neurofibroma of thyroid gland, one of which developed from thyroid capsule. Our patient most likely has primary neurofibroma of thyroid gland given the lack of syndromic features, however, genetic testing is needed in order to rule out NF1. In conclusion, clinicians should consider neurofibroma in their differential in cases of enlarging thyroid gland or nodules, especially in the presence of other clinical features. Presentation: 6/1/2024

6820 Assessing The Efficacy And Safety Of Setrusumab For Osteogenesis Imperfecta: Updated Phase 2 Data From The Phase 2/3 Orbit Study

Abstract Disclosure: G.S. Gottesman: Advisory Board Member; Self; Ultragenyx, Kyowa Kirin, Inc. Consulting Fee; Self; Ultragenyx. Research Investigator; Self; Alexion Pharmaceuticals, Inc., Ultragenyx. T.O. Carpenter: Advisory Board Member; Self; Ultragenyx. Consulting Fee; Self; Ultragenyx. Research Investigator; Self; Ultragenyx. M. Wallace: Advisory Board Member; Self; Ultragenyx. Consulting Fee; Self; Novosteo. P. Smith: Grant Recipient; Self; Ultragenyx. Research Investigator; Self; Ultragenyx. E.A. Imel: Consulting Fee; Self; Ultragenyx. Grant Recipient; Self; Ultragenyx. Research Investigator; Self; Ultragenyx. H. Wang: Employee; Self; Ultragenyx. Stock Owner; Self; Ultragenyx. H.M. Byers: Employee; Self; Ultragenyx. Stock Owner; Self; Ultragenyx. S. Krolczyk: Employee; Self; Ultragenyx. Stock Owner; Self; Ultragenyx. E.M. Lewiecki: Consulting Fee; Self; Amgen Inc, Radius Health, Inc. Grant Recipient; Self; Amgen Inc, Radius Health, Inc, Ultragenyx. Research Investigator; Self; Amgen Inc, Radius Health, Inc, Ultragenyx. Speaker; Self; Amgen Inc, Kyowa Kirin, Inc. Osteogenesis imperfecta (OI) is a rare genetic disorder characterized by bone fragility and low bone mass with no universally accepted treatment. Setrusumab is a fully human anti-sclerostin monoclonal antibody that improved bone mineral density (BMD), bone strength, and bone turnover markers in adults with OI (ASTEROID; NCT03118570). In the ongoing Phase 2/3 Orbit study (NCT05125809), Phase 2 evaluated the efficacy and safety of setrusumab in pediatric and young-adult cohorts with OI based on PK/PD, safety, and BMD data, to determine the dosing strategy for the Phase 3 portion. Subjects with OI Types I, III, or IV, ages 5 to <26 years, were randomized 1:1 to receive 20 or 40 mg/kg setrusumab intravenously monthly. Six-month data as of August 2023 are presented. Twenty-four subjects (50% female, 75% <18 years of age) with OI Type I (n=17/24, 71%) or III/IV (n=7/24, 29%) were enrolled and randomized to receive 20 mg/kg (n=14/24) or 40 mg/kg (n=10/24) of setrusumab. The mean (SD) baseline-corrected area under the effect curve (AUEC) for serum P1NP in the 20 mg/kg setrusumab group was 4153 (4407) µg/(L*day) over month one of treatment, and 5256 (5521) µg/(L*day) in the 40 mg/kg group. Mean (SE) change from baseline in lumbar spine BMD in the 20 mg/kg group was 9.1% (1.8%) and 12.8% (2.5%) at M3 and M6, respectively (all p<0.05 vs baseline) and 9.3% (2.4%) and 16.1% (3.9%) in the 40 mg/kg group (M6 p<0.05 vs baseline). Mean (SE) baseline BMD Z-score in the 20 mg/kg group of 2.1 (0.8) improved by 0.6 (0.8) at M3 and 0.9 (0.8) at M6, and improved from 1.1 (0.4) at baseline by 0.5 (0.4) and 0.9 (0.4) at M3 and M6, respectively, in the 40 mg/kg group (all p<0.05 vs baseline). The median annualized fracture rate (excluding fingers, toes, face, and skull) was reduced significantly from 0.7 to 0 (p=0.042) after setrusumab initiation (calculated reduction of 67%). No new radiographically confirmed fractures excluding fingers, toes, face, and skull were reported in 20/24 (83%) subjects after starting setrusumab, while only 4/24 (17%) reported fractures (precipitating events: one subject: slipped on ice, stubbed toe, one subject each: fell off of tricycle, bending over in bed, tripped and fell). Setrusumab treatment resulted in no unexpected adverse events. Treatment-related adverse events included infusion-related reaction (7/24, 29%), headache (3/24, 13%) infusion site pain, bone pain, and upper respiratory tract infection (each 1/24, 4%). In Orbit Phase 2, we observed significant improvements from baseline in lumbar spine BMD at M3 and M6 at both 20 and 40 mg/kg doses, with no marked differences between dose groups. Fracture rates significantly decreased with setrusumab initiation, with 83% of subjects reporting no new fractures. Presentation: 6/1/2024

7697 Co-existing Overt Cushing Syndrome And Primary Aldosteronism Secondary To Unilateral Adrenal Adenoma

Abstract Disclosure: R. Tarrazona - Dominisac: None. M. Lantican: None. J.B. Aragon: None. Overt Cushing's syndrome and primary aldosteronism are two uncommon yet distinct adrenal disorders. Rarely do they coexist, complicating diagnosis and management. Here, we present a case of a 42 year old woman with a complex clinical profile for the past 21 months, marked by amenorrhea, weight gain, abdominal enlargement, new-onset hypertension, hyperglycemia, proximal myopathy, easy fatigability, and difficulty concentrating. A comprehensive physical examination and endocrine work-up confirmed coexistence of Cushing’s syndrome and primary hyperaldosteronism due to a left adrenal adenoma. Laparoscopic unilateral adrenalectomy was performed as definitive treatment of the functional tumor which resulted in substantial clinical improvement thereafter. This case highlights the importance of precise diagnosis and appropriate management in rare combined disorders, ultimately ensuring favorable patient outcomes. Presentation: 6/1/2024

8082 Primary Hyperparathyroidism or Familial Hypocalciuric Hypercalcemia? Why Not Both?

Abstract Disclosure: C.A. Zmijewski: None. P.D. Greenberg: None. S.R. Saul: None. Background: Although considered two separate entities, primary hyperparathyroidism (PHPT) and familial hypocalciuric hypercalcemia (FHH) can present concurrently. Case: A 68-year-old male with hypertension was referred to Endocrinology for hypercalcemia and osteoporosis. The patient reported a long-standing history of intermittent hypercalcemia, first diagnosed at age 30 with a strong family history, both his father and son. He denied symptoms of hypercalcemia, history of nephrolithiasis and fractures, and was not taking calcium supplementations. Labs were notable for intermittent elevations in calcium, the highest being 10.9 mg/dL (8.5-10.5 mg/dL), in addition to phosphorus levels as low as 1.7 mg/dL (2.5-4.5 mg/dL). Vitamin D was replete at 50 ng/mL (32-100 ng/mL) and the highest parathyroid hormone (PTH) was 124 pg/mL (10-66 pg/mL). The 24-hour urine for calcium was 117 mg (100-300 mg) with a Ca/Cr 0.01. DEXA scan showed T scores -2.2 at the right femoral neck and -3.4 at the distal radius (Z score -2.3). Due to the significant osteoporosis, a work-up for secondary causes was completed and was unremarkable. The differential diagnosis for the osteoporosis, elevated parathyroid hormone, and intermittent hypercalcemia included PHPT vs FHH or possibly, a combination. Additional imaging included a renal ultrasound which was negative for nephrolithiasis, Sestamibi and 4D-CT which were both negative for a parathyroid adenoma. Genetic testing confirmed a mutation in the CASR gene. Due to the inability to localize a possible lesion, the decision was made to treat the osteoporosis with zoledronic acid. Conclusion: PHPT is a common endocrine disorder; approximately 100,000 people in the United States develop PHPT annually. Conversely, FHH is a rare endocrine disorder with an incidence rate of 1 in 78,000. PHPT occurs due to the over-secretion of PTH by one or more parathyroid glands. FHH is an inherited autosomal dominant disorder, most commonly due to an inactivating mutation in the calcium-sensing receptor (CASR) gene. Distinguishing PHPT from FHH is important because PHPT is cured with surgery while FHH does not require treatment. Hypercalcemia from FHH, as opposed to PHPT, is suggested by the absence of symptoms, a positive family history, normal or high PTH, and hypocalciuria. However, it can be challenging to separate the two especially in atypical presentations (PTH can be normal in PHPT and elevated in FHH, and Ca/Cr can be < 0.01 in PHPT). But what if these two conditions were to co-exist? Case reports have described patients with concurrent PHPT and FHH (parathyroid adenoma confirmed with pathology and CASR gene mutation confirmed with genetic testing). In these cases, parathyroidectomy can still be considered in co-existing PHPT and FHH to alleviate symptoms and prevent complications of hypercalcemia. Though a rare occurrence, PHPT and FHH have been shown to co-exist in prior case reports. Presentation: 6/1/2024

5118 When Thyroid Gland is Not Made of Thyroid Cells

Abstract Disclosure: A. Bulut: None. L. Ma: None. J.P. Noordzij: None. S.Y. Lee: None. Introduction: Neurofibroma is a type of peripheral nerve tumor that can arise sporadically or be a part of neurofibromatosis type 1 (NF1), a rare genetic disorder. Neurofibromas within the thyroid gland are extremely rare. Here, we present the fifth reported case of primary neurofibroma of thyroid gland. Case: A 60-year-old woman with history of systemic lupus erythematosus and hypertension presented with enlargement of left thyroid gland. She was diagnosed with Graves’ disease 40 years ago, which was treated with right thyroid lobectomy one year after the initial diagnosis. Five years after the surgery, she had recurrence of her symptoms and received radioactive iodine ablation with subsequent hypothyroidism. On presentation to endocrine clinic, she had thyroid ultrasound (US), which showed surgically absent right thyroid lobe and enlarged heterogenous left thyroid lobe measuring 5.1 cm x 3.8 cm x 3.9 cm with scant blood flow without discrete nodules. In interim, patient developed dysphagia and globus sensation. Repeat thyroid US showed enlargement of left lobe to 5.6 cm x 3.7 cm x 4.7 cm. Patient underwent completion thyroidectomy. Surgical pathology showed neurofibroma (S-100+, CD34+ and MSA-) without any thyroid parenchyma. Whole-body scan revealed no other evidence of tumors. Patient was referred for genetic analysis. Discussion: Neurofibromas are benign peripheral nerve system tumors primarily consist of Schwann cells along with other components of perineurium. They can occur as a sporadic lesion which accounts for 90% of solitary neurofibroma cases or be a part of NF1 on rare occasions. NF1 is an autosomal dominant genetic disorder due to germline mutation in NF1 gene located on chromosome 17q11.2, whose manifestations include café-au-lait macules, Lisch nodules, skeletal abnormalities, neurological deficits, and other benign and malignant tumors. Neurofibromas are the hallmarks of NF1. There are only few cases in the literature reported neurofibromas adjacent to or originating from thyroid gland. To the best of our knowledge, there have been only four other cases reporting primary neurofibroma of thyroid gland, one of which developed from thyroid capsule. Our patient most likely has primary neurofibroma of thyroid gland given the lack of syndromic features, however, genetic testing is needed in order to rule out NF1. In conclusion, clinicians should consider neurofibroma in their differential in cases of enlarging thyroid gland or nodules, especially in the presence of other clinical features. Presentation: 6/1/2024

7291 From Vaginal Bleeding to Genetic Complexity: McCune Albright Syndrome in a Toddler; Emphasizing Atypical Manifestations, Diagnostic Challenges, and Comprehensive Management

Abstract Disclosure: A.G. Martinez Sanchez: None. N. Fernandez: None. C.L. Bustamante Escobar: None. Background: McCune Albright Syndrome (MAS) is a rare genetic disorder characterized by a triad of peripheral precocious puberty, irregular café-au-lait spots, and bone fibrous dysplasia. It is often caused by post-zygotic somatic mutations in the GNAS1 gene. We present a case of a patient initially presenting with precocious puberty, whose diagnostic journey revealed MAS with atypical manifestations. Presentation: A 23-month-old girl was brought to the emergency department after her mother noticed vaginal bleeding during a diaper change; denied any trauma, fever, rash, or dysuria. Patient developed accelerated growth about six months earlier, followed by pubic hair three months prior and bilateral thelarche two weeks before presentation. The patient had no exposure to endocrine disruptors. The physical examination revealed a well-developed child, in the 92nd percentile for weight and 97th for height. Additionally, breast buds, fine hair on the labia, and minimal blood at the vaginal introitus, with no apparent signs of trauma. Initial laboratory findings showed prepubertal LH and FSH levels, elevated estradiol 120 pg/ml (prepubertal range <10) and advanced bone age (4.2 years). Normal levels of testosterone, 17-hydroxyprogesterone, and DHEA sulfate. Pelvic ultrasound demonstrated an enlarged uterus (5.6 x 1.8 x 2.4 cm) and a large cystic lesion (4.4 cm) on the right ovary. During a follow-up at the endocrinology department one week later, a meticulous examination identified an irregular café-au-lait spot measuring about 2cm over the occipital right side of her scalp. Further tests, including GnRH stimulation test, tumor markers (LDH, b-HCG, CEA, and Ca19-9), brain MRI and bone scan, yielded normal findings. Given the presentation consistent with Peripheral precocious puberty, Letrozole was initiated at 1.25 mg daily. Three months later, her growth velocity remained accelerated. However, there was a decrease in both breast tissue and uterus size (4.2 x 1.2 x 1.7 cm), and the ovarian cyst was resolved. Genetic testing in blood indicated no mutations. To conduct a thorough assessment, the insulin-like growth factor (IGF-1) level was measured and found to be 200 ng/mL (normal range 56-144 ng/mL). Unfortunately, obtaining prolactin levels was challenging due to difficult intravenous (IV) access. Conclusion: This case reveals the complexity of MAS in precocious puberty, emphasizing atypical features that add complexity to the diagnosis. Identifying an irregular café-au-lait spot served as a diagnostic indicator, revealing the diverse clinical presentations. The challenges of relying solely on genetic testing for diagnosis are evident due to the mosaic nature and tissue-specific distribution of the mutation, as highlighted by the absence of mutations in this patient. Long-term management requires ongoing monitoring and a multidisciplinary approach for optimal patient outcomes. Presentation: 6/1/2024

8412 Resolution of Central Hypothyroidism shortly after Transsphenoidal Surgery For Cushing’s Disease

Abstract Disclosure: L. Esper: None. A. Ibrahim: None. N. El Asmar: None. Background: Cushing's disease is a rare endocrine disorder characterized by excessive cortisol production, resulting in various metabolic disturbances. Hypercortisolism is known to cause central hypothyroidism. The mechanism is complex and involves hypercortisolism mediated decreased TRH and TSH secretion in addition to inhibition of peripheral deiodination. This case details the successful management and recovery of a patient with Cushing's disease and reversal of central hypothyroidism after pituitary surgery.Case:A 43-year-old man was evaluated for central hypogonadism, 20 pound weight gain with central weight distribution, and the development of purple abdominal striae for the past year. He had a normal thyroid exam and appeared euthyroid. He was alsodiagnosed with hypertension and prediabetes in the past yearrequiring medical therapy.A low dose dexamethasone suppression test (DST) resulted in AM cortisol of 12.9 mcg/dl. Two adequate 24hr Urinary cortisol measurements showed elevated cortisol excretion at 458 and 378mcg/24. Lab evaluation revealed elevated cortisol levels along with elevated adrenocorticotropic hormone (ACTH) levels(ACTH of 172 pg/ml with a cortisol level of 23.9 mcg/dl). A high dose DST demonstrated suppression of cortisol to 3.4 mcg/dl. MRI pituitary was performed which showed a clearright sided 7mm pituitary adenoma.Thyroid function tests performed were consistent with central hypothyroidism, with low levels of free thyroxine (FT4) at 0.67ng/dl along with an inappropriately low normal thyroidstimulating hormone (TSH) at 0.596 uIU/ml. Total T4 was low at 4 ug/dl in addition to a low total T3 of 66 ng/dl. Remaining labs revealed central hypogonadism along with slightly elevated prolactin of 16 ng/ml. He was not started on thyroid hormone.He then underwent transsphenoidal surgery for tumor removal. He developed post-operative adrenal insufficiency (cortisol 2.12 mcg/dl) 16 hours post-op after which he was started on hydrocortisone replacement, indicating remission. 12 hours post-op, his TSH was 0.656 uIU/ml with a free t4 of 0.79 ng/dl, both in the normal range. 36 hours post-op, TSH was 0.524 uIU/ml and free t4 was 1.15 ng/dl. Histopathological examination confirmed the diagnosis of an ACTH-secreting pituitary adenoma.At 4 weeks post-op, thyroid labs showed normal FT4 (1.07ng/dl) and TSH (2.06uIU/ml). Conclusion: Hypercortisolism causes a global inhibition of the thyroid axis, with decreased levels of TSH, T4, and T3 (1). Previous studies suggest the monitoring of thyroid function at 6 and 12 months after surgical cure of hypercortisolism. Our case suggests that the resolution of hypothyroidism occurs shortly after surgery for Cushing’s disease and the need for earlier monitoring. Presentation: 6/3/2024

7077 A Rare Case Of Hypophosphatasia Presenting With Osteoporosis In A Young Female Patient- Diagnostic Delay In Hypophosphatasia

Abstract Disclosure: R. Abdelmasih: None. I. Ali: None. Introduction: Hypophosphatasia is a rare hereditary cause of secondary osteoporosis that affects 1/100.000 individuals. The rate of osteoporosis due to hypophosphatasia is probably underestimated as it likely goes undiagnosed in heterogeneous or milder cases. We present a case of Hypophosphatasia that presented initially with osteoporosis and went misdiagnosed for years with intermittent treatment of Bisphosphonate, luckily with no atypical fractures that prompted different course of management for osteoporosis. Case Presentation: A 44-year-old female with a history of rheumatoid arthritis and osteoporosis diagnosed 7 years prior and treated with intermittent bisphosphonate which was discontinued due to side effects including muscle aches and bone pains, presented to our endocrinology clinic to establish care for osteoporosis. Patient denied prior fractures. She reported jaw pain that is being evaluated by otolaryngology and a dentist. Family history is negative. DEXA scan showed Z scores of -1.1, -1.8, and -2.2 of the lumbar spine, femoral neck, and total femur respectively. Laboratory workup showed consistently low alkaline phosphatase (ALP) 25, 20, <20 U/L (ref range 34-123), elevated Vitamin B6 of 167 nmol/L (ref range 20-125), normal parathormone, calcium, phosphate, Vit D, magnesium, and liver enzymes. Genetic testing was sent for Tissue non-specific alkaline phosphatase (TNALP). Hypophosphatasia was diagnosed based on clinical and laboratory findings, patient was started on Asfotase alfa. Clinical course is to be followed. Discussion: Hypophosphatasia is a rare hereditary disorder due to mutation of (TNALP). In normal induvial, TNALP breaks down pyrophosphate to phosphate. It also plays a role in transferring Vit B6 into the tissues. Hence, clinical presentation due to impaired calcium-phosphate hemostasis is broad including musculoskeletal pain, pseudofractues, dental abscess, and neurological symptoms (due to accumulation of Vit B6). The clinical picture varies depending on the heterogenicity of ALPL mutation. Genetic testing is not mandated to establish diagnosis, clinical presentation and laboratory testing including low ALP and elevated Vit B6 are sufficient. However, genetic testing and counseling are recommended for the patient’s sake and their family members. Antiresorptive bone therapy is contraindicated due to a further decrease of bone turnover with reported cases of increased risk of atypical femur fracture, Bone density is reported to improve with enzyme replacement therapy with bone-targeting recombinant alkaline phosphatase (Asfotase Alpha), if further treatment is needed, anabolic treatment is preferred. We present this case to shed light on such a rare disease to decrease rates of underdiagnosis or delayed diagnosis in young patients presenting with osteoporosis for prompt treatment and improved quality of life of these patients. Presentation: 6/2/2024

6864 Genetic Profile And Identification Of A Novel Mutation In PHEX In X-Linked Hypophosphatemia (XLH) Patients At A Brazilian Research Center: Insights And Implications

Abstract Disclosure: M. Monseff Rodrigues da silva: None. I.M. de Araújo: None. F.J. de Paula: None. Background: X-Linked Hypophosphatemia (XLH) is a rare genetic disorder characterized by low phosphate levels in the blood, primarily caused by mutations in the PHEX gene, leading to bone skeletal deformities and reduced quality of life. XLH genetics is extensively studied with over 500 pathogenic mutations in the PHEXgene having been identified. Common mutations include missense, nonsense, and splicing, accounting for approximately 50% of cases. However, genotype-phenotype correlations remain unclear. Methods: We conducted a cross-sectional study using a convenience sample selected from the osteometabolism an outpatient clinic in Brazil. Genetic analysis was performed using next-generation sequencing (NGS; Ilumina) in collaboration with Mendelics Laboratory. Results: In our study, 9 out of 10 patients showed previously known and reported mutations, with 60% exhibiting common mutation types. The mutations occur in different codons; however, the most prevalent consequence was the substitution of glycine (G) with adenine (A), present in 40% of the patients. One patient, however, showed a unique missense mutation in PHEX gene (arginine to glutamate at codon 266), which leads to a premature stop codon, a mutation absent in over 183,000 X chromosomes from XLH individuals. Even though this mutation was novel, no significant diferences in the phenotype of this patient were seen in comparision with the rest of the cohort. Discussion: The findings of our study underscore the genetic heterogeneity characteristic of XLH, as evidenced by the fact that 90% of our patient cohort exhibited mutations previously identified in the literature, with a significant 60% showing common mutation types. This highlights the recurring genetic patterns in XLH, which can be instrumental for diagnostic and - perhaps in the future - therapeutic strategies. Particularly notable is the predominant mutation involving the substitution of glycine with adenine, found in 40% of our patients, underscoring its potential role as a key mutation in the pathogenesis of XLH. Furthermore, the discovery of a novel missense mutation in one patient, resulting in a premature stop codon, enriches the mutation spectrum of XLH and suggests a deeper complexity in the genetic landscape of the disease. This mutation, not previously documented in the extensive database of over 183,000 X chromosomes from XLH individuals, opens new avenues for research into the disease's molecular mechanisms and potential genotype-phenotype correlations. Conclusion: This study underlines the genetic diversity within XLH, emphasizing the need for comprehensive genetic analysis to understand the full spectrum of the disease. More studies are yet necessary to elucidate if there is a genotype-phenotype correlation. Presentation: 6/1/2024

7407 Normosmic Idiopathic Hypogonadotropic Hypogonadism in Women: A Case Report and Comprehensive Review

Abstract Disclosure: E.G. Bustamante: None. M. Sulehri: None. I. Patoli: None. A. Karunakaran: None. Normosmic Idiopathic Hypogonadotropic Hypogonadism (nIHH) in Women: A Case Report and Literature ReviewIntroduction: IHH is a rare genetic disorder affecting gonadotropic-releasing hormone (GnRH) production and/or action, resulting in diminished sex steroid levels. Characterized by the absence of spontaneous pubertal development. In women, it manifests with normal adrenarche but absent thelarche and menarche. Our case highlight a late diagnosis of IHH in a 34-year-old woman with primary amenorrhea. Case report: A 34 year old lady with a history of primary amenorrhea sought evaluation. At age 16, she underwent assessment for short stature and primary amenorrhea, denying anosmia, headache, visual disturbances. Evaluation revealed bone age concordant with chronological age and normal MRI Brain. Pelvic ultrasound (US) showed small premenarchal uterus and ovaries. She initiated oral contraceptive pills (OCP) and experienced regular menses. Seeking fertility assistance at age 24, a normal Hysterosalpingogram was followed by successful delivery of twins after ovarian stimulation. Post-delivery menses did not resume and OCP was not restarted. Family history revealed a sister with irregular periods requiring OCP.Subsequently workup at age 30 showed Estradiol 22 pg/ml, FSH/LH 4.1/2.3 mUI/mL; normal PRL, TFT, DHEAS, 17OHP. Repeat Pelvic US showed normal uterus, endometrial stripe normal at 0.24 cm and non-visualized ovaries. PCOS testing negative for hyperandrogenism. Progesterone challenge resulted in no withdrawal bleeding. Brain MRI demonstrated a 2.2 x 1.3 mm hypoenhancing ovoid mass in the pars Intermedia of the pituitary gland suggestive of pituitary microadenoma. Pituitary axis hormonal testing was normal. Karyotype revealed 46 XX (normal female). Genetic evaluation identified a pathogenic variant (p.R35C) in GNRH1 gene. Her final diagnosis: nIHH. Discussion HH is diagnosed in 5% of all women with primary amenorrhea and is divided into 2 major categories: Kallmann syndrome and nIHH. The majority of known causes of HH can be attributed to mutations in KAL1, FGFR1, or GNRHR. The p.R35C variant has been associated with autosomal dominant nIHH. Diagnosis involves clinical suspicious, low LH/FSH and sex steroid levels, normal hypothalamic–pituitary imaging, and exclusion of differentials.Treatment goal for female focus on regular breast and uterine development, as well as the capability to conceive. Use of hormonal replacement therapy and/or gonadotropins or pulsatile GnRH for ovarian stimulation are essential. ConclusionWhile IHH predominantly affects men, limited literature explores its manifestation in women and its impact on fertility. The identification of a GNRH1-related nIHH variant highlights the role of genetic testing in specific HH diagnoses. Failure to diagnose in adolescence may compromise women overall well-being Presentation: 6/1/2024

8059 An Interesting Case Of Hypogonadism Likely Caused By Cushing's Syndrome

Abstract Disclosure: R. Ripa: None. J. Su: None. R. Patel: None. Introduction: Cushing’s Syndrome is a rare endocrine disorder that comprises a multitude of symptoms caused by hypercortisolism. Given non-specific symptoms, the disease can often be overlooked for more common diseases, such as diabetes, obesity, and even hypogonadism. Hypogonadism is a clinical disorder defined by decreased functional activity of the gonads. The diagnosis can often be challenging in developed males, who present with hypogonadotropic hypogonadism without an obvious cause. Here we present a case of a male who presented with hypogonadism symptoms for at least 5 years before being diagnosed with Cushing’s syndrome. Case Presentation: 58-year-old Caucasian male with a medical history of hypertension, cardiomyopathy and a BMI of 23, presented with decreased libido and erectile dysfunction. He was started on testosterone therapy three years prior, however it was discontinued due to heart failure. Without testosterone replacement, lab work was notable for: low free and total testosterone, 21.4 and 50.6 ng/dL, respectively, inappropriately normal findings of LH, FSH (1.0 and 4.9 IU/L, respectively), as well as unremarkable findings of GH, Prolactin, TSH, pituitary MRI and testes ultrasound, leading to a suspicion of hypogonadism. Due to persistent symptoms of hypogonadism and low testosterone, clomiphene was started but later changed to testosterone therapy after cardiology consultation. Shortly after, he began reporting facial flushing, associated with facial roundedness and elevated blood pressure. Upon further work up, hyperaldosteronism and pheochromocytoma testing was negative and his baseline cortisol was 21.9 mcg/dL with a low adrenocorticotropic hormone (ACTH), <5 pg/mL. Further, dexamethasone suppression testing showed suboptimally suppressed cortisol (14.4 mcg/dL). An abdomen MRI with and without contrast revealed a 2.3 cm adrenal adenoma, confirming an adrenal source of Cushing’s syndrome, and he underwent an adrenalectomy. Post-procedure, his cortisol and ACTH levels normalized to 10.5 mcg/dL and 39 pg/mL, respectively, showing a revival of his hypothalamic - pituitary - adrenal axis. Unfortunately, however, his free and total testosterone levels continued to remain low (38.9 and 152 ng/dL, respectively) and he was continued on testosterone therapy. Discussion: Our patient initially presented with decreased libido, and low testosterone levels and was treated for hypogonadism, as he did not have typical Cushing’s symptoms. Due to eventual weight gain and facial edema, it was only then that work up was pursued showing hypercortisolism release, leading to a proper diagnosis of Cushing’s syndrome. Hypercortisolism can affect all parts of the body, including hormones, muscles, joints and bones. When presenting in the initial stages and with mild symptoms, the diagnosis of hypercortisolism is often challenging and can go undetected for many years. Presentation: 6/2/2024

Klippel-Feil Syndrome Associated with Sprengel's Syndrome: A Rare Case Report

Klippel-Feil Syndrome (KFS) is a rare congenital disorder characterized by the fusion of cervical vertebrae, often associated with other anomalies such as Sprengel's deformity. We report the case of a 61-year-old female patient presenting with chronic neck pain and paresthesia in the lower limbs, worsened after a minor domestic accident. Cervical CT imaging revealed multisegmental vertebral fusion (C2-C3, C7-T1) and Sprengel’s deformity with an omovertebral bone. This case highlights the importance of early diagnosis and comprehensive imaging, including X-rays, CT scans, and MRIs, for the optimal management of KFS and its associated complications. Awaiting the correction before proceeding with the payment.