Postmenopausal Hyperandrogenism Associated With Synchronous Ovarian Brenner Tumor, Bilateral Leydig Cell Tumor, and Adrenal Mass.

Hyperandrogenism in postmenopausal females may arise from either ovarian or adrenal sources and can pose a challenging diagnostic dilemma. We present the case of a 66-year-old female with postmenopausal hyperandrogenism with virilization, adrenal incidentaloma, and concurrent finding of two extremely rare ovarian tumors, including bilateral Leydig cell tumor and Brenner tumor. Laboratory tests showed elevated testosterone and androstenedione and normal dehydroepiandrosterone sulfate (DHEAS). Response to 1 mg overnight dexamethasone suppression test demonstrated persistently elevated testosterone and incomplete suppression of androstenedione. Computed tomography (CT) scan showed a left adrenal nodule and an unremarkable appearance of the ovaries. The pelvic ultrasound did not show an ovarian tumor on the right ovary, and the left ovary was not seen. Adrenal and ovarian vein sampling suggested the ovaries as the source of the testosterone. Given the ovarian vein sampling results, a multidisciplinary discussion between endocrinology and gynecologic oncology concluded that bilateral salpingo-oophorectomy (BSO) was the next best step for diagnosis and management. Laparoscopic BSO was performed. Histopathology showed bilateral Leydig cell tumors and a left ovarian Brenner tumor. At one-year postoperative follow-up, alopecia improved, and testosterone level normalized. This case highlights the importance of diagnostic pathways and interdisciplinary collaboration in managing rare clinical scenarios of hyperandrogenism in postmenopausal females. As in our case, surgeons may be hesitant to remove normal-appearing ovaries. While the three presented tumor types in this case arise from distinct tissues and exhibit different histological characteristics, the presence of such a unique triad prompts consideration of potential unifying pathogenic mechanisms.

The Impact of Multicultural Interfacility Video Case Conference: A Novel Education Model After the COVID Pandemic.

Context: The COVID-19 pandemic challenged undertaking gradual educational activities for residency and fellowship trainees. However, recent technological advances have enabled broadening active learning opportunities through international online conferences. Objective: The format of our international online endocrine case conference, launched during the pandemic, is introduced. The objective impact of this program on trainees is described. Methods: Four academic facilities developed a semiannual international collaborative endocrinology case conference. Experts were invited as commentators to facilitate in-depth discussion. Six conferences were held between 2020 and 2022. After the fourth and sixth conferences, anonymous multiple-choice online surveys were administered to all attendees. Results: Participants included trainees and faculty. At each conference, 3 to 5 cases of rare endocrine diseases from up to 4 institutions were presented, mainly by trainees. Sixty-two percent of attendees reported 4 facilities as the appropriate size for the collaboration to maintain active learning in case conferences. Eighty-two percent of attendees preferred a semiannual conference. The survey also revealed the positive impact on trainees' learning regarding diversity of medical practice, academic career development, and confidence in honing of presentation skills. Conclusion: We present an example of our successful virtual global case conference to enhance learning about rare endocrine cases. For the success of the collaborative case conference, we suggest smaller cross-country institutional collaborations. Preferably, they would be international, semiannually based, and with recognized experts as commentators. Since our conference has engendered multiple positive effects on trainees and faculty, continuation of virtual education should be considered even after the pandemic era.

Lean Implementation for Graduating Optimally Controlled Stable Type 2 Diabetics from Endocrine Specialty Clinic Back to Primary Care.

INTRODUCTION: Endocrine specialty clinics (SCs) are occupied by a high percentage of stable follow-up patients, limiting access to new patients with greater needs. AIM: Feasibility project to improve access to diabetes SC by reducing the number of stable optimally controlled follow-up type 2 diabetic patients. SETTING: M Health Fairview (MHFV), a hybrid network of University of Minnesota academic and Fairview Health community hospitals and clinics with affiliated providers. PROGRAM DESCRIPTION: A team-based lean methodology quality improvement graduation program including medical assistants, nurses, physicians, and a compact with primary care (PC) was used to identify within the Endocrine clinic population the graduation-eligible optimally controlled stable type 2 diabetic patients, acclimate them to the graduation concept, engage in shared decision-making, and transition them back to PC with a warm hand-off and graduation certificate. PROGRAM EVALUATION: Seventeen percent (58/341) of eligible patients with optimally controlled diabetes graduated by 6 months, ranging between 0 and 83% per week. DISCUSSION: The innovation and feasibility of opening SC access through the use of a team-based graduation program to transfer stable diabetes patients back to their home clinic was demonstrated. This innovation has the potential to support health system triage of new patients to limited access specialty care.

High Thyroglobulin Antibody Following Intravenous Immunoglobulin Therapy in Athyreotic Differentiated Thyroid Cancer Patients.

American Thyroid Association guidelines recommend to follow athyreotic differentiated thyroid cancer patients with measurement of serum thyroglobulin and thyroglobulin antibody as tumor markers. The guidelines recommend that rising thyroglobulin or thyroglobulin antibody should prompt additional investigations and potentially additional therapies. Two patients with differentiated thyroid cancer who also received intravenous immunoglobulin are presented. Their cancer history, serial thyroglobulin and thyroglobulin antibody measurements and imaging findings relative to the time course of intravenous immunoglobulin treatment are illustrated. Acute rise in thyroglobulin antibody led to further imaging which did not show cancer progression. Additional history documented an intravenous immunoglobulin treatment exposure had occurred within the past one to two months before the increased thyroglobulin antibody measurement. Follow-up serial thyroglobulin antibody levels declined over time after the intravenous immunoglobulin exposure. Intravenous immunoglobulin, which is a pooled human serum product, contains thyroglobulin antibody. Commercially available thyroglobulin antibody assays may detect the thyroglobulin antibody contained within the administered intravenous immunoglobulin, leading to alarm and further imaging to exclude progressive malignancy. Thyroglobulin antibody rise and fall can be demonstrated in relationship to intravenous immunoglobulin time of administration. Thyroglobulin antibody is higher at time-points sooner than at later time-points following intravenous immunoglobulin treatments. Intravenous immunoglobulin may be a benign source of transiently high thyroglobulin antibody measured in the follow-up of differentiated thyroid cancer patients. Repeat thyroglobulin and thyroglobulin antibody testing one to two months following a higher level in a patient treated with intravenous immunoglobulin may avoid unnecessary imaging to look for progressive malignancy.

Acute elevation of interleukin 6 and matrix metalloproteinase 9 during the onset of pituitary apoplexy in Cushing's disease.

PURPOSE: Pituitary apoplexy is a rare endocrine emergency. The purpose of this study is to characterize physiological changes involved in pituitary apoplexy, especially during the acute phase. METHODS: A Cushing's disease patient experienced corticotroph releasing hormone (CRH)-induced pituitary apoplexy during inferior petrosal sinus sampling (IPSS). The IPSS blood samples from the Cushing's disease patient were retrospectively analyzed for cytokine markers. For comparison, we also analyzed cytokine markers in blood samples from two pituitary ACTH-secreting microadenoma patients and one patient with an ectopic ACTH-secreting tumor. RESULTS: Acute elevation of interleukin 6 (IL-6) and matrix metalloproteinase 9 (MMP9) was observed in the IPSS blood sample on the apoplectic hemorrhagic site of the tumor. In contrast, such a change was not observed in the blood samples from the contralateral side of the apoplexy patient and in other IPSS samples from two non-apoplexy Cushing's disease patient and a patient with ectopic Cushing's syndrome. CONCLUSION: IL-6 and MMP9 may be involved in the acute process of pituitary apoplexy in Cushing's disease.

Hypercalcemia, nephrolithiasis, and hypervitaminosis D precipitated by supplementation in a susceptible individual.

Vitamin D supplementation is common among the general public. Although generally considered safe, vitamin D supplement-induced toxicity has been reported, often in association with manufacturing or labeling errors. Additionally, selected patient populations may have a hypersensitivity to vitamin D supplementation, leading to consequences due to supraphysiologic serum 25-hydroxyvitamin D levels. A 58-y-old woman developed hypercalcemia and its sequelae while on vitamin D supplementation. Despite being vitamin D replete, a functional medicine practitioner prescribed vitamin D starting at 8000 IU/d, tapering to 2000 IU/d over 3 mo. Nephrolithiasis was diagnosed after 3 mo of vitamin D treatment. Laboratory testing revealed a high serum calcium, low parathyroid hormone (PTH), high 25-hydroxyvitamin D [25(OH)D] and high 1,25 dihydroxyvitamin D [1,25(OH)2D]. Further investigation demonstrated low serum 24,25 dihydroxyvitamin D [24,25(OH)2D] and a very high ratio of 25(OH)D to 24,25(OH)2D, leading to the consideration of loss of function mutation in cytochrome P450 (CYP)24A1, a key enzyme involved in the degradation of 25(OH)D and 1,25(OH)2D into inactive metabolites. This leads to the persistence of high levels of bioactive vitamin D metabolites, increasing the risk for development of intoxication with vitamin D supplementation. Vitamin D supplementation can precipitate hypercalcemia and nephrolithiasis in individuals with altered vitamin D catabolism. This highlights the importance of monitoring serum calcium levels in patients who are being supplemented with vitamin D.

Impact of molecular testing on thyroid nodule neoplastic diagnosis, stratified by 4-cm size, in a surgical series.

Whether molecular testing adds diagnostic value to the evaluation of thyroid nodules 4-cm or larger is unknown. The impact of molecular testing on cytopathologic-histopathologic diagnosis of neoplasm (adenoma or malignant), stratified by nodule size

Semiquantitative assessment of cytomorphologic features can predict mutation status of thyroid nodules with indeterminate cytologic diagnosis.

Molecular diagnostics increasingly direct the management of thyroid nodules with an indeterminate cytologic diagnosis. This study was undertaken to correlate cytomorphologic features with the molecular profiles in an effort to identify features predictive of molecular aberrations. One hundred eighty-nine thyroid nodules with an indeterminate thyroid cytology diagnosis (atypia of undetermined significance, suspicious for follicular lesion, and suspicious for malignancy) with an adequate sample submitted for targeted mutation detection by polymerase chain reaction or next-generation sequencing were assessed semiquantitatively for the following cytomorphologic parameters: cellularity, Hurthle cell changes, microfollicles, nuclear elongation, nuclear grooves, nuclear enlargement, nuclear atypia, extent of atypia, and colloid. Based on this evaluation, a cumulative cytomorphologic score (CCS) and a more simplified overall atypia score (OAS) were assigned to each case. Associations among mutational status and each of the aforementioned parameters, CCS, and OAS were determined. Of the 189 nodules with indeterminate cytology, 63 (33.3%) harbored at least 1 mutation. RAS and BRAF were the most common mutations, found in 34 (18.0%) and 13 (6.9%) cases, respectively. Both CCS and OAS were highly associated with the presence of all mutations (P < .0001) and with the presence of BRAF and RAS mutations in particular (all P < .01). Semiquantitative assessment of various cytomorphologic features in indeterminate thyroid cytology cases showed a strong association of higher OAS and CCS and incidence of BRAF and RAS mutations. Using a more objective approach to thyroid cytology can potentially decrease the overall number of indeterminate diagnoses, leading to fewer repeat procedures and unnecessary surgical procedures.

Coma in Thyroid Storm: Review of Aggregated English-Language Case Reports.

CONTEXT: Coma is a serious manifestation of thyroid storm (TS) about which little is known. OBJECTIVE: To describe the features, duration, treatment response, and prognosis of coma in the setting of TS. DESIGN: Aggregate analysis of individual English-language case reports of coma in the setting of TS from 1935 to January 2019. SETTING: Hospitals. PATIENTS: Sixty-five cases were identified, 29 from case reports and 36 from case series. INTERVENTIONS: Antithyroid drugs, corticosteroids, beta-blockers, iodine, intubation, plasmapheresis, antibiotics, thyroidectomy, radioiodine, dialysis, and l-carnitine. MAIN OUTCOME MEASURES: Awakening and death rates overall and in relation to administered treatments, day of coma presentation, and time from coma onset; symptoms associated with coma; TS and coma scales; thyroid and cerebrospinal laboratory tests; electroencephalogram; brain imaging; and autopsy results. RESULTS: Mortality was 38% in the setting of TS-related coma, 11% during the years 1978 to 2019 compared with 70% for 1935 to 1977. Both awakening and death commonly occurred within the first 2 days of coma onset. Reduction in total and free T4 values, and possibly also total T3 value, correlated with awakening from coma. Lower death rates were associated with use of antithyroid drugs, corticosteroids, beta-blockers, and intubation. Plasmapheresis was associated with awakening in 67% of cases but not with lower death rates. CONCLUSIONS: Prognosis of coma associated with TS remains poor. Current guidelines for the early use of plasmapheresis in unresolving TS are advocated and should be considered urgently at the point of confusion or delirium in an effort to abort coma.

Thyroid nodules over 4 cm do not have higher malignancy or benign cytology false-negative rates.

PURPOSE: Whether thyroid nodules 4 cm or larger with benign cytology carry a higher risk of malignancy, and should be managed differently than smaller nodules remains controversial. We aimed to evaluate the malignancy rate and benign cytology false-negative rate in thyroid nodules ≥4 cm compared with those <4 cm. METHODS: All thyroidectomies between January 2010 and December 2014 were reviewed. Patient demographics, preoperative sonographic nodule size, fine needle aspiration cytology (FNAC), and final surgical pathology results were compared for index nodules ≥4 vs. <4 cm. RESULTS: A total of 490 index nodules with preoperative FNAC were identified. A total of 137 nodules were ≥4 cm and 353 nodules were <4 cm. The prevalence of carcinoma was lower (23 vs. 53%) in nodules ≥4 vs. <4 cm (p < 0.0001). The false-negative rate of benign FNAC for ≥4 and <4 cm index nodule was 5.2% and 5.9%, respectively (p = 1.000). CONCLUSIONS: This study shows that thyroid nodules ≥4 cm do not have a higher malignancy rate at surgery nor higher benign cytology false-negative rate than smaller nodules. Thyroid nodules over 4 cm do not require resection, to rule out malignancy, based on size alone.

Cognitive functioning in thyroid cancer survivors: a systematic review and meta-analysis.

BACKGROUND: Some thyroid cancer (TC) survivors experience cognitive symptoms. PURPOSE: The purpose of this study is to perform a systematic literature review and meta-analysis comparing cognitive performance in TC survivors to controls. METHODS: We performed a seven-database electronic search and hand-search. We performed duplicate independent reviews and data abstraction. Random effects meta-analyses reported standardized mean differences (SMDs) with 95% confidence intervals (CIs), where a negative value implies worse performance in the TC group. RESULTS: We reviewed 1174 unique citations and 10 full-text papers. We included seven studies of 241 treated TC survivors and 273 controls. Cognitive function was statistically significantly worse in TC survivors in the following domains: Attention and Concentration (Digit Span Forwards) SMD - 0.37 (95% CI - 0.62, - 0.13, p = 0.003, four studies), Speed of Processing (Trail Making A) SMD - 0.36 (95% CI - 0.66, - 0.05, p = 0.022, four studies), and Language (Controlled Oral Word Association [COWAT]-Categories) SMD - 0.97 (95% - 1.31, - 0.64, p < 0.001, two studies). Executive Function results varied: COWAT-Letters SMD - 0.60 (95% CI - 0.94, - 0.27, p < 0.001, two studies), Digit Span Backwards SMD - 0.40 (95% CI - 0.64, - 0.15, p = 0.002, four studies), and Trail Making B test SMD - 0.20 (95% CI - 0.51, 0.10, p = 0.191, four studies). Statistical heterogeneity limited the COWAT-Categories and Digit Span Backwards meta-analyses. CONCLUSIONS: Cognitive function was worse in TC survivors in multiple domains. Limitations included few studies, potential confounding, and lack of prospective data. IMPLICATIONS FOR CANCER SURVIVORS: TC survivors may experience impairments in cognitive function and should report cognitive concerns to healthcare practitioners.

THYROID STORM WITH COMA IN A PATIENT WITH METASTATIC THYROID CARCINOMA AND GRAVES DISEASE: WON THE BATTLE BUT LOST THE WAR.

OBJECTIVE: To describe the background and events that may precipitate thyroid storm (TS) with coma as well as the course of treatment intervention and our patient's response to treatment. METHODS: We present a case of TS with coma including precipitants, thyroid function tests, thyroid ultrasound, computed tomography findings, course, treatment, and outcome. RESULTS: A 71-year-old woman was hospitalized with back pain and right leg weakness due to a newly diagnosed, 12.4-cm sacral tumor. The tumor had metastasized from poorly differentiated papillary thyroid carcinoma. The patient developed TS characterized by thyrotoxicosis with fever, tachycardia, and mental status change progressing to coma over several days. Treatment including antithyroid drugs, steroids, saturated solution of potassium iodide, L-carnitine, therapeutic plasma exchange, and thyroidectomy reversed the prolonged coma and TS, but left residual flaccid quadriplegia. The patient eventually died. CONCLUSION: This patient presented with multiple rare causes of TS (computed tomography contrast and Graves disease in the setting of high-volume thyroid cancer) and a rare manifestation of TS (coma). The TS included fever, tachycardia, and rapid onset of prolonged coma in the setting of thyrotoxicosis. Precipitants of the TS may have included enlarged thyroid tissue from goiter, distant metastasis, the operation, computed tomography contrast exposure, and high levels of thyroid-stimulating immunoglobulin. Multifaceted treatments, most importantly therapeutic plasma exchange, resolved the coma and TS, but the patient still succumbed to comorbidity. We agree with the Japan Thyroid Association recommendation for therapeutic plasma exchange in patients with TS, especially those in a coma who do not awaken within 24 to 48 hours of starting conventional TS treatment.

Significant Loss of Areal Bone Mineral Density Following Prolonged Bed Rest During Treatment With Teriparatide.

We present of a case of severe osteoporosis with thoracic myelopathy secondary to nontraumatic T8 compression fracture managed nonsurgically with 3.5 months of bed rest. Despite treatment with teriparatide starting at initial presentation, 1-year follow-up dual energy x-ray absorptiometry scan revealed a significantly greater than expected 19% reduction in lumbar spine bone mineral density (BMD) and a 6% reduction in total hip density. Daily alcohol consumption, severe osteoporosis at baseline, and immobilization secondary to transient myelopathy treated with strict bed rest all likely contributed to unexpected BMD findings.

Association of Biotin Ingestion With Performance of Hormone and Nonhormone Assays in Healthy Adults.

Importance: Biotinylated antibodies and analogues, with their strong binding to streptavidin, are used in many clinical laboratory tests. Excess biotin in blood due to supplemental biotin ingestion may affect biotin-streptavidin binding, leading to potential clinical misinterpretation. However, the degree of interference remains undefined in healthy adults. Objective: To assess performance of specific biotinylated immunoassays after 7 days of ingesting 10 mg/d of biotin, a dose common in over-the-counter supplements for healthy adults. Design, Setting, and Participants: Nonrandomized crossover trial involving 6 healthy adults who were treated at an academic medical center research laboratory. Exposure: Administration of 10 mg/d of biotin supplementation for 7 days. Main Outcomes and Measures: Analyte concentrations were compared with baseline (day 0) measures on the seventh day of biotin treatment and 7 days after treatment had stopped (day 14). The 11 analytes included 9 hormones (ie, thyroid-stimulating hormone, total thyroxine, total triiodothyronine, free thyroxine, free triiodothyronine, parathyroid hormone, prolactin, N-terminal pro-brain natriuretic peptide, 25-hydroxyvitamin D) and 2 nonhormones (prostate-specific antigen and ferritin). A total of 37 immunoassays for the 11 analytes were evaluated on 4 diagnostic systems, including 23 assays that incorporated biotin and streptavidin components and 14 assays that did not include biotin and streptavidin components and served as negative controls. Results: Among the 2 women and 4 men (mean age, 38 years [range, 31-45 years]) who took 10 mg/d of biotin for 7 days, biotin ingestion-associated interference was found in 9 of the 23 (39%) biotinylated assays compared with none of the 14 nonbiotinylated assays (P = .007). Results from 5 of 8 biotinylated (63%) competitive immunoassays tested falsely high and results from 4 out of 15 (27%) biotinylated sandwich immunoassays tested falsely low. Conclusions and Relevance: In this preliminary study of 6 healthy adult participants and 11 hormone and nonhormone analytes measured by 37 immunoassays, ingesting 10 mg/d of biotin for 1 week was associated with potentially clinically important assay interference in some but not all biotinylated assays studied. These findings should be considered for patients taking biotin supplements before ordering blood tests or when interpreting results. Trial Registration: clinicaltrials.gov Identifier: NCT03034707.

Hypothyroidism in late-onset Pompe disease.

PURPOSE: In Pompe disease, a deficiency of acid α-glucosidase enzyme activity leads to pathologic accumulation of glycogen in tissues. Phenotype heterogeneity in Pompe includes an infantile form and late-onset forms (juvenile- and adult-onset forms). Symptoms common to all phenotypes include progressive muscle weakness and worsening respiratory function. Patients with late-onset forms of Pompe disease commonly complain of chronic fatigue and generalized muscle weakness prior to being diagnosed with Pompe disease, and this may lead to consideration of hypothyroidism in the differential diagnosis. This study aimed to evaluate the prevalence of hypothyroidism in the adult-onset form of Pompe disease. METHODS: Electronic chart review was performed at the Advanced Therapies Clinic at the University of Minnesota Medical Center (UMMC) to identify patients with late-onset Pompe disease. The identified charts were reviewed for a co-diagnosis of hypothyroidism. A query was made to the clinical data repository at UMMC searching diagnosis ICD9 code 244.9 (hypothyroidism not otherwise specified) and/or presence of levothyroxine from 2011 to 2014 in patients 18 years of age and older. RESULTS: The clinical data repository found a prevalence of hypothyroidism of 3.15% (56,072 of 1,782,720 patients) in the adult patient population at UMMC. Ten adult patients with Pompe disease were identified, five with the diagnosis of hypothyroidism (50%, 95% CI: 23.7, 76.3, p < 0.001 compared with the general UMMC adult population). CONCLUSIONS: Hypothyroidism was found at a higher prevalence in patients with late-onset Pompe disease compared to the general adult population at UMMC. Studies in larger populations of patients with Pompe disease would be needed to confirm an association of Pompe disease and hypothyroidism. Challenges include finding an adequate sample size, due the rarity of Pompe disease.

Correlation Between Histological Diagnosis and Mutational Panel Testing of Thyroid Nodules: A Two-Year Institutional Experience.

BACKGROUND: Indeterminate thyroid fine-needle aspiration (FNA) cytology, including atypia of undetermined significance (AUS/FLUS) and suspicious for follicular neoplasm (SFN), continues to generate uncertainty about the presence of malignancy, resulting in repeated follow-up, repeat FNA, or diagnostic surgery. Mutational panel testing may improve the malignancy risk prediction in indeterminate nodules, but the general application of such testing has not been investigated extensively. METHODS: A retrospective review was performed of all patients undergoing thyroidectomy at a tertiary care facility over a two-year period. Mutational panel test results, when present, were analyzed relative to FNA cytologic result and surgical histopathologic diagnosis. Malignancy rates, sensitivity, specificity, positive predictive values (PPV), negative predictive values (NPV) and positive and negative likelihood ratios (LR) were calculated. RESULTS: A total of 261 operated thyroid nodules had the following initial FNA cytology results: 2% non-diagnostic, 23% benign, 28% AUS/FLUS, 11% SFN, 9% suspicious for malignancy (SUSP), and 27% malignant. The histopathologic malignancy rate was 48%, subcategorized by cytology into benign 7%, AUS/FLUS 30%, SFN 38%, and SUSP 83%. Mutations were more frequent in indeterminate nodules that were histologically malignant versus benign (p < 0.0001) or versus adenoma (p = 0.001). Mutational analysis in 44 AUS/FLUS nodules resulted in a malignancy detection sensitivity of 85%, a specificity of 65%, a PPV of 50%, a NPV of 91%, and a positive LR of 2.4. In 12 SFN nodules analyzed with ThyroSeq(®) testing, sensitivity was 100%, specificity 57%, PPV 63%, NPV 100%, and LR 2.3. Performance of the seven-gene mutational panel was not significantly different from the ThyroSeq(®) panel in the AUS/FLUS group. The malignancy yield, comparing the mutation positive AUS/FLUS group with the untested AUS/FLUS surgical cohort, did not reach statistical significance (p = 0.17). CONCLUSIONS: In a surgical cohort, a similar NPV but a lower PPV was found with the use of mutational panel testing compared to the published literature. Following the identification of a mutation, the prevalence of malignancy in the AUS/FLUS or SFN category was increased by nearly 15% to 45% and 53%, respectively. Further study is needed to confirm these results and to analyze clinical outcome subcategories relative to the utility of mutational testing.

Bosma arhinia microphthalmia syndrome: Clinical report and review of the literature.

Bosma arhinia microphthalmia syndrome (Bosma syndrome)(OMIM 603457) is a congenital condition characterized by microphthalmia with coloboma, arhinia and endocrine findings in the setting of normal intelligence and brain structure. This condition is quite rare with fewer than 50 case reports and series. Although pathogenesis is presumed to be genetic, the cause remains unknown. We report an individual with Bosma syndrome who had bilateral colobomatous microphthalmia, arhinia, high arched palate, mild ear malformations, and hypogonadotropic hypogonadism requiring growth hormone treatment in childhood, and normal intelligence. Clinical evaluation was significant for a geometrically abnormal aorta with effacement of the sinotubular ridge, a finding not previously reported in this condition. An MRI revealed absent olfactory bulbs. Suggested criteria for diagnosis of Bosma should include arhinia, hypoplastic maxilla, normal cognition, and hypogonadotropic hypogonadism in males.