Endocrinological Evaluation Research Articles

Evaluación endocrinológica del paciente con enfermedad nodular tiroidea

Llamamos nódulo tiroideo a aquella lesión concreta palpable o radiológicamente distinguible del parénquima tiroideo. La enfermedad nodular tiroidea tiene una prevalencia progresivamente creciente a medida que ha mejorado la calidad de las técnicas de imagen, principalmente la ecografía. El objetivo de la presente revisión es señalar cuales son los pasos en la evaluación endocrinológica del paciente con enfermedad nodular tiroidea. Más concretamente, cual es la mejor estrategia coste/efectiva para diagnosticar los nódulos tiroideos malignos. Tras una buena anamnesis y exploración clínica, el estudio se completa con una determinación de TSH y la realización de una ecografía tiroidea, que es la prueba diagnóstica que más criterios aporta para poder hacer la indicación de PAAF. La muestra obtenida se estudiará según el sistema Bethesda.

Clinical investigation of pituitary incidentalomas: A two-center study.

Recent advances in imaging technology resulted in an increase in pituitary incidentalomas (PIs) detection. PIs were reported to be present in 1.6% persons with magnetic resonance imaging of the brain. Whereas, there were few studies about PIs with detailed investigation. We aimed to investigate the clinical and endocrinological characteristics of PIs. We evaluated 65 patients diagnosed with PIs who underwent detailed clinical and endocrinological evaluations. Of the 65 patients, 33 (50.8%) had non-functional pituitary adenomas (NFPAs), 11 (16.9%) had Rathke's cleft cysts (RCCs), 7 (10.8%) had functional pituitary adenomas (FPAs), 6 (9.2%) had benign extra-pituitary tumors (BEPTs), and 8 (12.3%) had malignant tumors (MTs). Compared with patients with NFPAs, those with MTs were significantly younger and had a significantly lower body mass index, lower prevalence of hypertension, and lower prevalence of dyslipidemia. Patients with MTs had significantly higher prevalence of central diabetes insipidus than those with NFPAs. In addition, patients with NFPAs had significantly higher prevalence of pituitary apoplexy than those with FPAs, BEPTs, and MTs. In conclusion, our study demonstrated clinical and endocrinological characteristics of PIs. Highly detailed clinical and endocrinological investigations should be performed for PIs. In addition, MTs should be considered in the differential diagnosis for young and lean patients with central diabetes insipidus.

Radiologic, genetic, and endocrine findings in isolated congenital nasal pyriform aperture stenosis patients

BackgroundCongenital nasal pyriform aperture stenosis (CNPAS) is a rare cause of upper airway obstruction in neonates. It can occur either associated with a solitary median maxillary central incisor (SMMCI) in 40–75% of cases or as an isolated morphogenic variant. Brain MRI is routinely performed in patients with CNPAS with a SCMMI due to the concomitant risks of intracranial midline defects of the hypothalamic-pituitary axis (HPA), holoprosencephaly, or associated endocrine dysfunction. However, the role of routine brain imaging and endocrinologic evaluation in patients with isolated CNPAS is not frequently studied given the assumption that isolated CNPAS is unlikely to be associated with any intracranial findings. ObjectivesTo evaluate intracranial findings on dual brain MRI imaging in isolated CNPAS patients and to determine if any radiologic, endocrinologic, or genetic abnormalities existed in these patients. MethodsWe performed a single-institution retrospective review and case series of patients with isolated CNPAS from 2006 to 2019. Findings from dual brain MRI imaging, cytogenetic and karyotype testing, and formal endocrinologic testing were analyzed for each patient and compared to reported findings in isolated CNPAS patients within the literature. ResultsFrom 2006 to 2019, 16/29 patients were identified at our institution with isolated CNPAS. Inpatient otolaryngologic consultation, CT, and brain MRI imaging was obtained after a mean postnatal age of 3.21 days, 13.5 days, and 35.91 days, respectively. Dual brain MRI imaging was obtained in 12/16 (75%) patients. In our patients, abnormal MRI findings included hypothalamic hamartoma, pars intermedius cyst, and grades 1 and 4 germinal matrix hemorrhages. No holoprosencephaly was found in any patient. Genetic testing was performed on 10/16 (62.5%) patients. Karyotyping was normal in all patients and microarray testing was abnormal in 2/10 patients that represented a 2p16.3 deletion in one patient and a 7q36 deletion causing an unbalanced translocation mutation of the Sonic Hedgehog gene in the second patient. In the latter patient, a hypothalamic hamartoma and panhypopituitarism was found. Endocrine evaluation was performed in 5 patients and was normal in 3/5 patients. ConclusionsOur case series of isolated CNPAS patients identified multiple abnormalities on radiologic, genetic, and endocrine testing; one of which that involved a defect of the HPA with panhypopituitarism resulting from a hypothalamic hamartoma. Based upon our findings, dedicated brain MRI imaging, endocrinologic, and genetic testing, should likely be considered for any newly diagnosed, isolated CNPAS patient given the uncommon but potential risk for associated intracranial abnormalities.

Preoperative and postoperative features of non-functioning pituitary adenomas: a single center experience

Objectives: The main purposes of surgical treatment for non-functioning pituitary adenomas are removal of the pressure on the surrounding structures, especially the hypophyseal gland and visual tissue, and the normalization of hypophyseal functions. In our study, we retrospectively reviewed postsurgical follow-up of patients with non-functioning pituitary adenoma treated at our institution in a period of 15 years of monitoring and evaluated surgical success, complication rate and recurrence rates in accordance with the literature. Methods: This study included 55 patients who had undergone surgery between 2000 and 2014 and who were followed-up postoperatively at our center. Preoperative and postoperative anterior pituitary hormones, complete resection and recurrence and also postoperative recovery of endocrinological and ophthalmological functions were statistically evaluated using file data of the patients. Results: There were 33 (60%) males and 22 (40%) females. It was observed that the adenoma caused pressure on the optic chiasm in 11 patients and infiltrated cavernous sinus in 9 patients. Postoperative mean follow-up was 75.14 ± 43.01 months. Seventeen (30.9%) patients had recurrence after complete resection. Postoperative persistence and deterioration rates were 12.2% and 26.6% in adrenal insufficiency, 12.2% and 26.6% in central hypothyroidism, respectively, while 12.2% worsening in central hypogonadism. Ophthalmologic findings were resolved in 62.5% of patients and persisted in 37.5% of the patients. Conclusions: The adenoma size and experience of the surgeon in non-functioning pituitary adenomas are the most important factors affecting surgical success. We recommend that operations should be performed in experienced centers, preoperative and postoperative endocrinological evaluations and long-term follow-up should be done.

Cushing Disease Masquerading as Glaucoma

Glaucoma is a well-recognized side effect of corticosteroids. However, steroid-induced glaucoma typically refers to that caused by exogenous corticosteroid administration. Glaucoma secondary to endogenous overproduction of corticosteroids has only been reported in a few case reports. We aim to bring attention to glaucoma as a rare but important manifestation of endogenous hypercortisolism. Patient history, physical exam, laboratory results, and imaging studies were reviewed. We report a case of glaucoma as the initial presentation of Cushing disease (CD). The patient was diagnosed with glaucoma 16 months prior to his endocrinology evaluation. At our initial encounter, the patient had a cushingoid appearance. Levels of 24-hour urinary cortisol and late-night salivary cortisol were elevated. Serum cortisol was not suppressed by 1 mg of dexamethasone overnight, but it was suppressed by 8 mg of dexamethasone. Adrenocorticotropic hormone was also elevated. All other pituitary hormone axes were unremarkable (thyroid-stimulating hormone, free thyroxine, follicle-stimulating hormone, luteinizing hormone, growth hormone, prolactin, and insulin-like growth factor). Pituitary magnetic resonance imaging suggested a small adenoma (2 to 3 mm); therefore, the patient underwent inferior petrosal sinus sampling. The results were consistent with CD. Transsphenoidal resection was performed and final pathology confirmed an adrenocorticotropic hormone-positive adenoma. Hypercortisolism and intraocular pressures improved after the surgery. Glaucoma can lead to irreversible blindness if left untreated or uncontrolled. However, endogenous hypercortisolism-induced glaucoma can be reversed with treatment of the underlying CD. Thus, heightened awareness of extraocular manifestations of secondary causes of glaucoma such as endogenous hypercortisolism is necessary in order to promote prompt evaluation and treatment.

Overweight Patients Less Improved Kidney Function After Laparoscopic Surgery for Adrenocortical Adenoma With Excess Cortisol Secretion.

Purpose: Glucocorticoid (GC) is known to be involved in the deterioration of kidney function both directly by affecting the glomeruli and renal tubules and indirectly by affecting cardiovascular function. Autonomous GC secretion is the main feature of primary adrenal hypercortisolism (PAHC). However, the ideal treatment option (operation vs. medical treatment and observation) for patients with PAHC has not been established yet. In this study, we assessed a time series of kidney function in patients with PAHC treated via laparoscopic adrenalectomy and investigated the predictive factors for kidney function 1 year after surgery.Methods: From September 1997 to July 2017, 175 laparoscopic adrenalectomies were performed for adrenal tumors at Akita University. Thirty patients, who were diagnosed as having PAHC via preoperative endocrinological evaluations and followed up for at least 1 year after surgery, were included in this study. Patients with severe complications or simultaneous aldosteronism were excluded. The mean age of the 30 patients was 57.5 years (range, 33–79 years; males, 4; females, 26), and the right and left sides were affected in 9 and 21 patients, respectively.Results: In all, 18 patients were diagnosed as having Cushing's syndrome and 12 as having subclinical Cushing's syndrome. The steroid cover was required in all cases after surgery. The estimated glomerular filtration rate significantly improved (78.4 mL/min [64.8–95.8] vs. 84.1 mL/min [66.8–104.0], p = 0.012) 1 year after surgery. Patients showing 5% or more improvement in kidney function and those showing less than 5% improvement were compared. On performing univariate analyses, factors such as a longer operative time, heavy body mass index (BMI), and preoperative unsuppressed ACTH were associated with worse improvement in kidney function. No significant associations were observed regarding metabolic disorders, clinical symptoms, and gross proteinuria. On multivariate analysis, patients with a higher BMI (≥ 24 kg/m2) showed worse improvement in kidney function at 1 year after surgery (odds ratio 14.0, 95% confidence interval 1.3–142.9, p = 0.012).Conclusions: In PAHC patients, after 1 year of follow-up, kidney function improved in terms of estimated glomerular filtration rate. Therefore, this improvement seems to be delayed in overweight patients, suggesting its direct role in renal function.

Physical, histological, endocrinological and steroidogenical evaluation of male cats postnatally exposed to sexual steroids

To test the hypothesis that postnatal sexual steroids induce an impairment of domestic male cat reproductive function, this study describes the physical, endocrine, steroidogenical and histological effects of a single, high dose of a postnatal sexual steroid in this species. Twenty male kittens were randomly assigned within the first 24 h of birth to: Testosterone enanthate 12.5 mg sc (TE; n = 8), medroxyprogesterone acetate 10 mg sc (MA; n = 6), or Placebo sc (PL; n = 6). The cats were followed until puberty when they were castrated. Kittens achieved puberty without age differences among groups (P > 0.05). Two MA cats presented abnormal testicular descent. Histological evaluation of the MA (P < 0.01), but not of TE testes revealed decreased diameter (P < 0.01) and epithelial height (P < 0.01) of the seminiferous tubules. Leydig cell nuclear area was also reduced in this group. Conversely, tubular/intertubular ratio was increased in TE animals (P < 0.01). Quantitative real-time PCR analysis of mRNA expression of testicular tissue revealed no significant differences among groups for StAR, CYP17A1 and androgen receptors. TE animals showed decreased CYP19A1 mRNA expression (P < 0.05). In the first 4 postnatal weeks, fecal testosterone (T) values were high, basal and intermediate in TE, MA and PL (P < 0.05), respectively. These differences progressively diminished and the three groups presented basal T concentrations from the 7th week on (P > 0.05). It was concluded that the postnatal progestagen initially suppressed the gonadal axis and caused an impairment of spermatogenesis and testicular descent at puberty. Androgen treatment caused downregulation of the final steroidogenic cascade.

MON-354 Undiagnosed Addison's Disease as a Cause of Infertility

Background: There are multiple potential mechanisms for infertility in AD (Addison’s disease) including suppression of HPG axis, LFOR (low functional ovarian reserve) secondary to AH (adrenal hypoandrogenism) or concomitant autoimmune POF (premature ovarian failure), as well as suppressive effect from high 17-OHP (17α-hydroxyprogesterone). Nonetheless, there is scarce literature concerning this complication of AD. Clinical Case: A 28 year old female with a normal BMI and a history of hypothyroidism, suspected PCOS, and spontaneous abortion presented to RE (Reproductive Endocrinology) for a 2 year history of primary infertility. She had menarche at age 12, with regular menses for 6 years until OCP was initiated. At age 24 she spontaneously conceived, but unfortunately miscarried. She subsequently developed oligomenorrhea, reporting menses every 3-4 months in the absence of hirsutism or acne. Initial evaluation demonstrated negative β-hCG, normal TSH 1.27 mcIU/ml (0.27-4.2), high anti-TPO antibodies 1040 IU/ml (<34), progesterone 12.79 ng/ml (0.06-0.89 follicular, 1.83-23.9 luteal), AMH 13.5 ng/ml (1.03-11.1), and 17-OHP 272 ng/dl (<80 follicular, <285 luteal), and low DHEA-S 20.6 mcg/dl (98.8-340) and free testosterone 1.6 pg/ml (0.16.4). AFC (antral follicle count) was 50, and semen analysis and HSG were unrevealing. Elevated 17-OHP was thought to represent luteal phase, but repeat in early follicular phase remained elevated, prompting referral to Endocrinology. Co-syntropin stimulation test was performed with pre-ACTH 17-OHP persistently elevated (546 ng/dl), with minimal increase 1 hour post-ACTH (598 ng/dl). Cortisol failed to stimulate increasing only from 11 to 14 mcg/dl post-ACTH. Further evaluation revealed elevated ACTH (324 pg/ml), and positive anti-adrenal antibodies. Following diagnosis of AD, HC (hydrocortisone) 10 mg in the morning and 2.5 mg in the afternoon was initiated with improvement in menstrual regularity to 34 day cycles. RE recommended initiation of letrozole for ovulation induction, and intrauterine insemination. However, given improvement in cycles with HC, Endocrinology recommended delaying fertility treatments temporarily. Four months after HC initiation, pregnancy was confirmed, and she subsequently delivered a healthy baby girl. Conclusion: This case emphasizes the importance of a thorough endocrinologic evaluation in patients with infertility, particularly those with other autoimmune endocrinopathies. The etiology of infertility in AD is likely multifactorial, and there is minimal supportive literature to date. While some authors have proposed LFOR secondary to adrenal hypoandrogenism or POF as an underlying etiology, this unique case describes a patient with high AMH and AFC, who had successful conception and pregnancy following initiation of HC replacement.

SAT-609 Plasmapheresis as Salvage Treatment in a Patient with Amiodarone-Associated Thyroid Dysfunction

Introduction: Treatment with amiodarone is associated with thyroid dysfunction. Thyrotoxicosis is a possible consequence and 3 types of amiodarone-induced thyrotoxicosis (AIT) are commonly defined: AIT1 (Iodine-induced hyperthyroidism), AIT2 (hyperthyroidism resulting from destructive thyroiditis) and mixed/indefinite forms resulting from a mixture of types 1 and 2. Treatment consists of thionamides or glucocorticoids, depending on the AIT type. Subsequently, thyroidectomy should be considered. Plasmapheresis has been mentioned as a "life-saving" treatment, although its use is not yet a standard practice in the resolution of thyrotoxicosis. Case report: 61-year-old man, with history of NYHA class II/III ischemic heart failure, submitted to cardiac resynchronization therapy defibrillator in 2014, permanent atrial fibrillation, dyslipidaemia, ex-smoker and COPD. No history of thyroid pathology. His usual medication included amiodarone 200mg od. On February of 2018, the patient entered the emergency room due to anginal pain that developed for cardiorespiratory arrest (CRA) and reverted after cardioversion. He was admitted to the Coronary Unit where an analytical study showed TSH - 0.01 μUI/mL, FT4-4.21ng/dL. Endocrinology evaluation was requested. The patient presented with digital tremor, without exophthalmia and a nodule was perceptible on palpation. It was prescribed thiamazole 30mg/day because of the suspicion of AIT 1. He performed thyroid ultrasonography with doppler that showed isoechoic nodule of 14mm in the right lobe, aspects suggestive of thyroiditis and preserved vascularization of the gland. Anti-thyroid and anti-TSH receptor antibodies were absent. Thus, the hypothesis of AIT 2 was more likely to occur and prednisolone 20mg/day was added, aiming to achieve euthyroidism that would provide the necessary conditions for the patient to undergo total thyroidectomy. From this moment on, FT4 and TSH assays were repeated every 3 days and prednisolone and thiamazole doses were increased to a maximum of 70mg and 40mg, respectively. Approximately 50 days after the onset of hospitalization, due to the inability to achieve euthyroidism and also to the progression of the heart disease that motivated a new CRA during the admission, total thyroidectomy was mandatory and therefore it was decided to proceed to plasmapheresis. The procedure went without any harm and a FT4 of 1,82 ng/dL was reached. This value was above the reference range, however with a marked improvement compared to the value prior to the procedure. The patient was then submitted to total thyroidectomy but died 2 days later due to multiorganic dysfunction. Conclusion: This case shows the difficulties that are often found in the treatment of AIT. Still, it makes clear that in urgent cases, plasmapheresis can be a viable and effective alternative in the restoration of euthyroidism, with the potential to save lifes.

SUN-LB073 Giant Prolactinomas: Recidive (Case Report)

Introduction: Prolactinomas are rare in childhood and adolescence. The signs and symptoms depend on age, sex, and tumor size and prolactin level. Case report: We present a case of 25-year-old patient diagnosed at age 13 with giant prolactinomas. He came to our observation after then neurosurgery was performed for symptoms of tumor expansion. Elements of sella turcica were not recognizable on the pituitary X-Ray. The CT described a large tumour of the pituitary gland. No pituitary insufficiency was observed after surgery but persistent hyperprolactinemia. Dopamine-agonist therapy was required postoperatively. After five years the patient developed normal puberty, reaching a final high=172cm. After seven years of prolactin level control and no IRM signs of recidive under medical therapy, we lost follow-up. After another 12 years, IRM described a 2/1.3/2.5 cm tumor residue with extension in the right cavernous sinus, PRL levels was high. Cabergoline therapy was reinitiated. Discussions: Neurosurgery was performed before endocrinological evaluation but was not curative. Dopamine-agonists were needed postoperatively. As a result of the favorable evolution of the normalization of the PRL and the disappearance of the pituitary tumor under treatment with cabergoline (seven years), after the interruption of the therapy, at a distance the recurrence occurred. In prolactinomas, first-line treatment is represented by dopamine-agonists. Surgery is reserved for patients resistant to medical therapy and those with severe neurological symptoms at diagnosis. Conclusions: In the case of macroprolactinomas, annual follow-up is required at the long term. In the event of recurrence of symptoms, biological or radiological, therapy with dopamine-agonists is required Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

SAT-LB066 Clinical Characteristics of Incidentally Discovered Functioning Adrenal Tumors: Study of Advancing Care and Pathogenesis of Intractable Adrenal Diseases in Japan (ACPA-J)

Objectives: Pheochromocytoma and paraganglioma (PPGL), Cushing syndrome (CS), bilateral macronodular adrenal hyperplasia (BMAH) and adrenocortical carcinoma (ACC) are rare adrenal tumors. Hence, collaboration of researchers and clinicians from several institutes and constructing patient registry are important to achieve progress in clinical management. We organized a research group and constructed a patient registry system for adrenal tumors named Advancing Care and Pathogenesis of Intractable Adrenal Diseases in Japan (ACPA-J). In the present study, we focused on incidentally discovered adrenal tumors despite the functioning tumors in ACPA-J database, and investigated their clinical characteristics. Subjects and methods: Clinical data of 176 patients with PPGL, 110 patients with CS, 38 patients with BMAH and 45 patients with ACC who were diagnosed 2006-2016 were registered to ACPA-J database by August 2018. Among the patients who have hormone excess confirmed by endocrinological evaluation, we analyzed the clinical characteristics of an incidentaloma (I) group and a non-incidentaloma (non-I) group in which their tumors were found based on signs and symptoms of adrenal disease, and compared those between two groups. Results: The hormone excess was confirmed in 162 patients with PPGL, 110 patients with CS, 38 patients with BMAH and 36 patients with ACC. Of those, 53.2% of PPGL, 36.7% of CS, 76.5% of BMAH and 24.5% of ACC were incidentaloma, respectively. Age in I group was higher in PPGL, CS and ACC compare to that in non-I group. Tumor size was larger in I group than that in non-I group only in ACC. Incidences of metabolic complications (hypertension, glucose intolerance and hyperlipidemia) were not different between two groups in all type of tumor. In PPGL, urine metanephrine levels and normetanephrine levels were not different between two groups. In CS and BMAH, morning plasma (p-) ACTH levels and p-cortisol levels in the morning, the midnight and after dexamethasone suppression test were not different between two groups. A rate of patients with subclinical cortisol excess was 13% in I group and 14% in non-I group in BMAH, whereas that in I group (50%) was higher than that in non-I group (23%) in ACC. Conclusions: The adrenal incidentaloma is defined as the tumor unexpectedly found during work-up for an indication unrelated to suspected adrenal disease. Most of the functioning adrenal tumors accompany signs and symptoms of hormone excess and have to be discovered in the process of work-up for adrenal disease. Our result showed there was not particular difference in characteristics between the incidentalomas and the non-incidentalomas. It was suggested that adrenal functioning tumors could be frequently overlooked. (This research was supported by AMED; JP18ek0109352, the Grant for NCGM; 30-A-1008, Health Labour Sciences Research Grant 2018.) Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

MON-393 Neuroblastoma Masquerading as Pheochromocytoma

Peripheral neuroblastic tumors (PNTs) are a group of tumors arising from sympathetic ganglion cells. It is a malignancy of childhood and rare in adults. The incidence in adulthood is only 0.12-0.2 cases per million per year. A 37 year old male presented with acute exacerbation of low back pain which started months prior to admission. MRI of the lumbar spine revealed a 3.6 x 3.4 cm lobulated heterogeneous mass-like lesion involving his right adrenal gland therefore, endocrinology evaluation was requested but not completed. He was a non-smoker without any significant past medical or surgical history and was not on any medications. On examination, He was normotensive and appeared to be in moderate distress. He had tenderness over the right sacroiliac joint. His renal and liver functions were normal. Serum metanephrines were normal however, normetanephrines were elevated to 501 pg/mL (< or = 148 pg/mL). Urine normetanephrines were 3,192 ug/day (88-444 ug/d), Urine volume of 3 L, total metanephrines of 3,342 ug/d (140-785 ug/d). Chromogranin A was 1,379 ng/mL (0-95 ng/mL). DHEAS, 17- hydroxyprogesterone, androstendione, and ACTH were normal. CT of his abdomen and pelvis with contrast showed a lobular heterogeneous mass involving the right adrenal gland with an increased size of 4.9 x 4.3 cm measuring 55 Hounsfield Units (HU). Right iliac core needle biopsy was done to evaluate his diffuse osseous metastasis which showed crush artifact, with positive chromogranin and synaptophysin staining. Right posterior pelvic crest lesion excision biopsy showed primitive small round cell neoplasm with neuroendocrine features, favoring an adult type neuroblastoma confirmed by immunohistochemical staining. He received chemotherapy and radiation and prior to debulking surgery, we initiated doxazosin. Surgery revealed a 6 cm neuroblastoma with extraadrenal extension. Iodine 123-metaiodobenzylguanidine (I-123 MIBG) showed extensive diffuse osseous metastatic disease. His catecholamines declined after surgery. Bone marrow (BM) involvement was noted and he underwent bone marrow transplantation with clinical improvement six months post-transplant. Although pediatric neurblastoma has a 91% survival rate, rates progressively decline to 40% in adults aged 25-64 years. Metastatic dissemination occurs in up to 40% of adults, mainly in the bone and BM as seen in our case therefore, adults should have a BM assessment upon diagnosis. Main issue is differentiation between PNTs and pheochromocytoma, that might be challenging due to variable imaging characteristics of PNTs and secretion of catecholamines in up to 70% of PNTs. On the other hand, catecholamines can be used as tumor markers for monitoring. Majority of adult PNTs are high-risk tumors with poor prognosis. No guidelines for adult management exists due to the rarity of the disease.

MON-352 Feminizing Adrenal Adenoma in an Adult Man Presenting with Gynecomastia and Hypogonadism

Introduction: Feminizing adrenal tumors (FAT) are a rare cause of gynecomastia and hypogonadism in men. Most FATs are malignant and secrete other adrenal hormones and precursors. Rarely, benign adenomas solely secreting estrogens have been described. We present a patient with an estrogen-secreting adrenal adenoma with benign histology without secretion of other hormones or precursors. Case: A 43-year-old man presented with complaints of fatigue and erectile dysfunction for 24 months and painful bilateral breast growth for 12 months. Mammography revealed bilateral gynecomastia, and he was initially treated with tadalafil for erectile dysfunction. Due to persistent symptoms, labs were obtained revealing a low total testosterone level of 56 ng/dL (250-827 ng/dL). Further labs were obtained after an endocrinology evaluation: total testosterone 28 ng/dL, estradiol 44 pg/mL (≤29 pg/mL), estrone 192 pg/mL (≤68 pg/mL), estriol <0.10 ng/mL, FSH 0.8 mIU/mL (1.6-8.0 mIU/mL), and LH 3.1 mIU/mL (1.5-9.3 mIU/mL). Serum prolactin, β-hCG, AFP, ACTH, TSH and IGF-1 were all within normal ranges. Testicular ultrasound showed a left-sided varicocele. Adrenal protocol CT showed a 2.8 cm left adrenal nodule with characteristics of an adenoma (round, homogenous, pre-contrast Hounsfield units: 10, absolute washout: 68%). DHEAS, androstenedione, 11-deoxycortisol, 17-hydroxprogesterone, renin and aldosterone were all within normal ranges. 24-hour urine for cortisol, metanephrines and 17-ketosteroids were normal. He underwent laparoscopic left adrenalectomy. Pathology revealed a 2.5 cm well-circumscribed adrenal adenoma. Features favoring a benign histology included <1 mitotic figure/50 HPF, no atypical mitotic figures, no necrosis, and no capsular invasion. Repeat hormonal workup after surgery showed total testosterone 223 ng/dL, free testosterone 58 pg/mL (35-155 pg/mL), estradiol 16 pg/mL, estrone 39 pg/mL, and FSH 3.3 mIU/mL. On follow-up, the patient reported improvement in fatigue, decreased breast tenderness, and a slight decrease in breast size. Discussion: FATs most commonly present with painful gynecomastia and hypogonadism in males. Cosecretion of other adrenal hormones or precursors is suggestive of malignancy. Most FATs are malignant, and benign adenomas solely secreting estrogen are extraordinarily rare. Unfortunately, a benign appearance on histology may not predict a benign course. A case was previously reported with a young male child with FAT and initial benign histology, who later developed malignant metastases several years after the initial surgery. This demonstrates the importance of post-operative surveillance with imaging and serial hormonal evaluations.

Radiological and endocrinological evaluations with grading of hypothalamic perifocal edema caused by craniopharyngiomas.

Hypophysial and hypothalamic dysfunction caused by craniopharyngioma is a serious problem despite the progress of surgical approaches and techniques. Perifocal edema induced by craniopharyngioma could be speculated as a potential factor resulting in pre- and post-operative hypophysial and hypothalamic dysfunction, as well as, their anatomical involvement. Medical records of 54 patients with craniopharyngioma were retrospectively reviewed. The edema was characterized by a hyperintense area in magnetic resonance imaging, being classified into no edema (group A), only adjacent to the tumor (group B), and extending to the internal capsule or the optic tract (group C). Age, sex, tumor diameter, presence of cyst, hydrocephalus, intracranial pressure (ICP) elevation, visual function impairment, hypopituitarism, diabetes insipidus, memory disturbance, and obesity were investigated. The occurrence rate of edema was found more frequently in adults (73.7%) than in children (25.0%). The peritumoral edema grading system had an excellent correlation with the degree of hypothalamic involvement graded by the Puget's system. Pre-operative ICP elevation was significantly detected in group C when compared with the other groups. In adults patients, group C was significantly associated with the occurrence of hydrocephalus both in pre- and post-operatively. Pre- and post-operative hypothalamic dysfunction, including diabetes insipidus, memory disturbance, and obesity, were highest in group C. Hypothalamic dysfunctions greatly influence the quality of daily living following craniopharyngioma surgery. The grading of perifocal edema's extension could be a new index suggesting pre- and post-operative hypothalamic dysfunction caused by craniopharyngioma in addition to their anatomical involvement.

Neonatal Hypopituitarism: Approaches to Diagnosis and Treatment

Hypopituitarism is defined as a decreased release of hypophyseal hormones, which may be caused by disease of the pituitary gland disease or hypothalamus. The clinical findings of neonatal hypopituitarism depend on the causes and on presence and extent of hormonal deficiency. Patients may be asymptomatic or may demonstrate non-specific symptoms, but may still be at risk for development of pituitary hormone deficiency over time. Patient history, physical examination, endocrinological, radiological and genetic evaluations are all important for early diagnosis and treatment. The aim of this paper was to present a review of etiological factors, clinical findings, diagnosis and treatment approaches in neonatal hypopituitarism.

Risk factors affecting post-pubertal high serum follicle-stimulating hormone in patients with hypospadias

Purpose The factors affecting spermatogenesis in adulthood in patients with hypospadias (HS) are not clearly understood. In the present study, risk factors affecting post-pubertal high serum follicle-stimulating hormone (FSH) were evaluated in patients with HS.Materials and methodsAmong those with a history of HS surgery, patients in whom endocrinological evaluation regarding pituitary–gonadal axis was performed at 15 years of age or older between March 2004 and April 2018 were enrolled in the present study. High serum FSH was defined as greater than 10 mIU/ml. The severity of HS was divided into mild and severe. Factors affecting the post-pubertal high serum FSH were estimated.ResultsSeventy-nine patients were included in the present study. The severity of HS was mild in 35 and severe in 44. History of undescended testis (UDT) was confirmed in 12. High serum FSH was detected in nine. On logistic regression model analysis, a history of UDT was the only significant factor for high serum FSH. The incidence of high serum FSH in patients with UDT was significantly higher than that in those without UDT (58.3% vs 7.5%, p < 0.01). When stratified by severity of HS and the presence of UDT, high serum FSH was detected in 70% in patients with severe HS and UDT, whereas less than 10% in other groups.ConclusionsA history of UDT was a significant factor for post-pubertal high serum FSH in patients with HS. Accordingly, the presence of UDT may be a marker for impaired spermatogenesis in patients with HS, especially in severe cases.

Assessment of pituitary function in patients with nasopharyngeal carcinoma: The effect of radiotherapy

Radiotherapy (RT) plays a very important role in nasopharyngeal carcinoma (NPC). The pituitary gland can be affected by radiation due to its proximity to the nasopharyngeal cavity. Our aim is to demonstrate the effect of radiotherapy given for NPC on anterior pituitary function with basal pituitary hormones and provocative tests. Patients with NPC that were treated with definitive chemoradioherapy were reviewed retrospectively. Serum ACTH, GH, PRL, FSH, LH, TSH and cortisol, DHEAS, IGF-1, E2, testosterone, fT3, fT4 levels were recorded to evaluate pituitary function. Insulin tolerance test was performed to investigate hypothalamic-pituitary-adrenal axis and GH -IGF-1 axis. Comparison between early tumor stage and advanced tumor stage for pituitary dysfunction was done. The median time interval between the RT and endocrinologic evaluation was 4.0 (1-13) years. ACTH deficiency was found to be most common hormonal problem with a frequency of 73.7%. Of these 71.4% were mild adrenal deficiencies. GH deficiency was seen in 60% of patients. fT3, TSH, GH and IGF-1 levels were significantly lower in patients with advanced tumor stage compared with early tumor stage (p = 0.033, p = 0.022, p = 0.043, p = 0.022, respectively). Growth hormone deficiency was found in all of advanced and in 43% of early tumor stage patients (p = 0.017). We found higher rates of ACTH and GH deficiencies followed by gonadotropin, corticotropin and thyrotropin deficiency. Basal pituitary hormones will not be sufficient to evaluate anterior pituitary failure. Annual and systematic dynamic tests together with basal anterior pituitary hormones would be needed.

Hypomagnesemia presenting as hypertensive urgency and multiple focal seizures in an infant

A fourty eight day old baby boy presented with a history of unprovoked, left sided focal seizures commencing at the age of 21 days of life and had recurrent hospital admissions previously. He was referred to our tertiary care centre for further evaluation. Clinical assessment on the day of presentation in the Emergency Room revealed a GCS of 13/15, without any focal neurological deficits and an anterior fontanelle that was level, but pulsatile. He was also noted to have severe hypertension. Laboratory parameters revealed hypocalcemia, hypomagnesemia and significantly low 25- OH- vitamin D levels with normal complete blood counts, liver and renal functions. Further endocrinology evaluation revealed a normal PTH level with increased fractional excretion of magnesium in urine. Seizure control was achieved with intravenous calcium and magnesium administration along with antiepileptic drugs. Hypertensive urgency needed appropriate management with nifedipine and labetalol initially and blood pressures normalized only after correction of serum magnesium levels. At discharge, all antihypertensive drugs could be tapered and discontinued. This interesting case highlights the issue of hypomagnesemia manifesting as hypertension, even up to levels of a hypertensive urgency in infants and children.

The impact of hypocalcemia on full scale IQ in patients with 22q11.2 deletion syndrome.

Hypocalcemia has been reported in ~50% of patients 22q11.2DS and calcium regulation is known to play a role in neuronal development and synaptic plasticity. Because calcium ions play a role in neuronal function and development, we hypothesized that hypocalcemia would be associated with adverse effects on full scale IQ index (FSIQ) in patients with 22q11.2DS. A retrospective chart review cataloguing the presence or absence of hypocalcemia in 1073 subjects with a laboratory confirmed chromosome 22q11.2 deletion evaluated at the Children's Hospital of Philadelphia was conducted. 852/1073 patients had an endocrinology evaluation with laboratory confirmed calcium levels. 466/852 (54.7%) had a diagnosis of hypocalcemia. 265/1073 subjects ranging from 0 to 51 years of age had both calcium levels measured and a neuropsychological evaluation yielding a FSIQ. The mean FSIQ for 146/265 patients with hypocalcemia was 77.09 (SD = 13.56) and the mean FSIQ for 119/265 patients with normocalcemia was 77.27 (SD = 14.25). The distribution of patients with intellectual disability (ID) (FSIQ<69), borderline IQ (FSIQ 70-79), and average IQ (FSIQ>80) between the hypocalcemic and normocalcemic groups was not statistically significant (χ2 = 0.2676, p = 0.8748). Neonatal hypocalcemic seizures were not found to be associated with ID. We found no difference in FSIQ between the hypocalcemic and non-hypocalcemic patients with 22q11.2DS. As our findings differ from a previous report in adult subjects, we speculate that this may reflect a potential benefit from early treatment of hypocalcemia and may support early 22q11.2 deletion detection in order to offer prompt diagnosis and subsequent treatment of hypocalcemia.

Immune-Related Thyroiditis with Immune Checkpoint Inhibitors.

Although immune-related thyroiditis (irT) with immune checkpoint inhibitors (ICI) is a common consequence, its natural course and management recommendations are not well characterized in existing guidelines. This study sought to investigate the evolution of irT and describe its course and sequelae. This was a retrospective study of cancer patients treated with ICI between November 2014 and July 2016 at MD Anderson Cancer Center and referred for endocrinology evaluation for suspected irT. Patients included had normal baseline thyroid function tests prior to starting ICI and developed thyrotoxicosis due to irT. Of 657 patients treated with ICI during the study period, 43(6.5%) met the inclusion criteria. ICI included: ipilimumab + nivolumab (40%), nivolumab (33%), pembrolizumab (21%), and other (7%). Cancer diagnoses observed were melanoma (23%), renal-cell carcinoma (21%), lung cancer (19%), bladder cancer (12%), colon cancer (9%), and other cancers (15%). Median time from ICI start to thyrotoxicosis was 5.3 weeks (range 0.6-19.6 weeks). Clinically, patients presented with painless thyroiditis, and 67% were asymptomatic during the thyrotoxicosis phase. Thyrotoxicosis lasted a median of six weeks (range 2.6-39.7 weeks). Hypothyroidism developed in 37 (84%) patients at a median of 10.4 weeks (range 3.4-48.7 weeks) after starting ICI. These patients remained on levothyroxine and ICI at a median follow-up of 57.4 weeks (range 1-156.7 weeks) from hypothyroidism onset. Four patients recovered without initiating levothyroxine and remained euthyroid at a median follow-up of 11.35 months (range 4.43-14.43 months). Subgroup analysis of ipilimumab + nivolumab versus nivolumab alone showed a median time to thyrotoxicosis of two weeks [confidence interval (CI) 3.5-8.4] versus six weeks ([CI 1.2-2.8]; p = 0.26) and time to hypothyroidism of 10 weeks [CI 8.1-11.9] versus 17 weeks ([CI 8.8-25.2]; p = 0.029) after starting ICI. Thyroid peroxidase and thyroglobulin antibodies were present in 45% and 33% at the time of irT diagnosis. IrT manifests as an early onset of thyrotoxicosis, which is largely asymptomatic, followed by rapid transition to hypothyroidism requiring long-term levothyroxine substitution. The evolution of irT is more rapid with combination ICI. Frequent monitoring of thyroid function tests during ICI is warranted. Future guidelines need to recognize this entity and incorporate their management.