European Journal Of Endocrinology Research Articles

7692 Morning Cortisol Levels In Patients With Established Primary Adrenal Insufficiency

Abstract Disclosure: A. Prete: Research Investigator; Self; Diurnal. V. Theiler-Schwetz: Research Investigator; Self; Diurnal. W. Arlt: Research Investigator; Self; Diurnal. I.O. Chifu: Research Investigator; Self; Diurnal. B. Harbeck: Research Investigator; Self; Diurnal. C. Napier: Research Investigator; Self; Diurnal. J.D. Newell-Price: Research Investigator; Self; Diurnal. A. Rees: Research Investigator; Self; Diurnal. N. Reisch: Research Investigator; Self; Diurnal. G.K. Stalla: Research Investigator; Self; Diurnal. N. Aslam: Employee; Self; Diurnal. H. Coope: Employee; Self; Diurnal. K. Maltby: Employee; Self; Diurnal. J. Porter: Employee; Self; Diurnal. J. Quirke: Employee; Self; Diurnal. R.J. Ross: Consulting Fee; Self; Diurnal. Background: Primary adrenal insufficiency (PAI) is rare: prevalence ∼100-140/million and incidence 4:1 000 000/year in Western societies [1]. The diagnosis of PAI is suggested by an early-morning cortisol <140 nmol/L (5 µg/dL) [1]. The commonest cause in adults is autoimmunity (∼90% in Western countries) and it is generally considered progressive once the diagnosis is made, although it has been reported that residual cortisol secretion is present in ∼30% of patients 2. We have developed a modified-release formulation of hydrocortisone to replace the physiological cortisol circadian rhythm and are undertaking a Double-Blind, Double-Dummy, Two-Way Cross-Over, Randomised, Phase II Study of Modified-Release Hydrocortisones: Chronocort® Versus Plenadren® in PAI. During recruitment, we were surprised by the number of patients who were ineligible as they had detectable morning cortisol levels. Methods: Main inclusion criteria: Participants with known PAI on stable glucocorticoid replacement therapy and an early morning pre-dose cortisol <50 nmol/L (1.8 µg/dl). Baseline serum cortisol was taken at ∼0700h and measured in a central laboratory by ADVIA Centaur® immunoassay with the lower limit of detection <14nmol/l (<0.5 µg/dL). Results: 86 patients with PAI (autoimmune aetiology in 71), median age 52 years (range 20-73), 60 female, were screened in 8 centres in UK and Germany. 18 (21%) patients were excluded from the study based on morning cortisol >50 nmol/L (1.8 µg/dL), and of those 68 patients who qualified on the main inclusion criteria 51 (59% of screened) had a cortisol <14 nmol/L (<0.5 µg/dL). Of the 18 patients (autoimmune aetiology in 10) excluded based on their morning cortisol level, 9 (50%) were female and 11 (13% of screened), had morning cortisol ≥140 nmol/L (5.0 µ/dL). 12 patients with morning cortisol of >50nmol/L (1.8 µ/dL) were retested and only 2 then qualified; their initial morning cortisol levels were 70 and 51 nmol/L. In patients retested the median difference between retest and the initial sample was 13 nmol/L (range 1-421 nmol/L). Conclusions: In patients with an established diagnosis of PAI, the majority had undetectable morning cortisol, but cortisol was detectable in 41% of patients and above 140 nmol/L in 13% confirming previous publications 2. Retesting patients with a cortisol >50nmol/L showed very similar results suggesting that the detectable cortisol was not an artefact and likely due to background cortisol secretion. 1. Bornstein SR, et al. J Clin Endocrinol Metab 2016;101:364-89.2.Pearce SHS, et al. European Journal of Endocrinology (2021) 184, R61–R67 Presentation: 6/1/2024

O-04 A diagnostic riddle of an adrenal incidentaloma

Abstract Clinical case A 78-year-old male underwent preoperative CT as transcatheter aortic valve implantation was planned. In addition to a 6 cm incidental mass in the right adrenal, it also revealed unspecific pulmonary nodules. The patient was referred to the Endocrine unit. Non-contrast adrenal CT demonstrated a heterogenous 6 cm tumor, < 10 HU. The patient had a history of psoriasis, type 2 diabetes mellitus, hypertension, chronic kidney disease, atrial fibrillation, peripheral artery disease, aortic stenosis and coronary artery disease. Clinical examination revealed no signs of Cushing's syndrome. First, normal blood metanephrine/normetanephrine concentrations confirmed that pheochromocytoma was ruled out. The possibility of a metastatic tumor mass was investigated by tumor biopsy, histopathology was compatible with an adrenocortical neoplasm, Ki67 2%. Further laboratory work-up is given in Table 1. How should the laboratory findings be interpreted? Primary aldosteronism was ruled out. Cortisol was not suppressed on 1mg DST, in contrast to perfectly normal 24h urinary free cortisol. Late night salivary cortisol (LNSC) was markedly increased, 1210 nmol/l and low ACTH concentration further suggested true hypercortisolism. Does the patient suffer from hypercortisolism? The patient had no clinical signs of Cushing syndrome, albeit cardiometabolic diseases. False positive DST and LNSC results were suspected. Indeed, the patient was using 1% hydrocortisone lip lotion. On repeat screening after discontinuation of hydrocortisone, LNSC was 3.8 nmol/l, and DST remained positive (258nmol). The patient was diagnosed with autonomous cortisol excess (MACS) (1). Should the patient undergo surgery for the right adrenal mass? MACS in combination with relevant co-morbidities and large tumor size indicated surgery (1), which the patient consented to. After surgery, cortisol concentrations remained suppressed which prompted hydrocortisone replacement therapy. Final pathology review classified the tumor as an adenoma, Weiss Score 0/9 and Ki-67 2%. Conclusion False positive cortisol screening tests are common and must be ruled out before surgery. For DST, common explanations are exogenous glucocorticoid use, drugs that accelerate dexamethasone metabolism and estrogen induced increase in CBG. The most common pitfalls for LNSC are deranged circadian rhythm and exogenous hydrocortisone. Reference (1). Fassnacht el al. European Society of Endocrinology clinical practice guidelines on the management of adrenal incidentalomas. European Journal of Endocrinology,2023; 189(1): G1–G42.Table 1

PMON78 Improvement in Resistant Hypogonadism with use of Clomiphene in Prolactinomas Treated with Dopamine Agonist: A Case Study and Review of Literature

Abstract Introduction Prolactinomas account less than half of all pituitary adenomas and cause persistent hypogonadism and infertility despite treatment with dopamine agonists such as cabergoline or bromocriptine and improvement of prolactin levels (Gillam 2006). Conventional therapy for persistent hypogonadism in males is testosterone supplementation but this can cause fluctuations in serum testosterone levels and inhibition of spermatogenesis and infertility. Clomiphene citrate has been used to treat infertility and hypogonadism in males and females for over 50 years. Below we present a patient with persistent hypogonadism and review of available literature while on cabergoline with improving prolactin levels being treated with clomiphene Case Report A 21-year-old Caucasian male presented to our clinic after being diagnosed with macroadenoma measuring 1.6 x1.7×1.8 cm without stalk compression. Further pituitary functional work up was normal except for elevated prolactin levels of 232 ng/mL and total testosterone level of 107 ng/dL and free testosterone level of 4.1 ng/dL. Patient was started on cabergoline and titrated according to prolactin levels. Despite being on high dose cabergoline, 3.5 mg weekly, and improvement of prolactin levels (Prolactin level 53 ng/mL), he continued to have persistent hypogonadism (Total Testosterone 188 ng/dL and Free Testosterone 8.5 ng/dL) along with hypogonadal symptoms. Patient expressed his desire to preserve his future fertility and was uncertain he could use gel or self-inject replacement therapy therefore clomiphene citrate 25 mg tablet daily was started. Repeat testosterone levels six weeks later normalized (Testosterone 532 ng/dL and Free Testosterone 19 ng/dL) and symptoms improved. Treatment was continued with subsequent testosterone levels remained stable along with improved prolactin levels over the last year. Discussion/Conclusion A prospective study of hypogonadism in 14 males treated for prolactinomas with dopamine agonist showed 71% of patients responded to clomiphene treatment with improved testosterone levels and symptoms (Ribeiro 2009). A second study done by Vilar et al in 2018 of similar hypogonadal males on dopamine agonist treatment for prolactinomas showed 72% improvement in symptoms and testosterone levels over 12 weeks of clomiphene treatment. Our case, along with reviewed literature, showed that clomiphene is an effective alternative treatment option for resistant or persistent hypogonadism in male patients with prolactinomas being treated with dopamine agonists. References Gillam, M. P., Molitch, M. E., Lombardi, G., & Colao, A. (2006). Advances in the treatment of prolactinomas. Endocrine Reviews. https://doi.org/10.1210/er.2005-9998Ribeiro, R. S., & Abucham, J. (2009). Recovery of persistent hypogonadism by clomiphene in males with prolactinomas under dopamine agonist treatment. European Journal of Endocrinology, 161(1), 163–169. https://doi.org/10.1530/EJE-09-0084Vilar, L., Lyra, R., The, A. C., Trovao, E., Gadelha, P., Albuquerque, L. (2018). The role of clomiphene citrate in the resolution of hypogonadism in male patients with prolactinomas under cabergoline therapy. 20th European Congress of Endocrinology. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Neuroinfundibulitis: Pituitary Stalk Thickening Presenting as Diabetes Insipidus

Background: Isolated pituitary stalk thickening (PST) from neuroinfundibulitis is a rare entity that requires thorough evaluation of secondary causes and understanding of treatment options. Clinical Case: A 55-year-old male presented with progressive polyuria and polydipsia over several months. He had no significant head injuries, headache, weight loss, fatigue or inability to exercise. His serum sodium level was 148 (135 - 145 mmol/L) with a serum osmolality 310 (275-305 mOsm/kg), and urine osmolality was 246 (40-1200 mOsm/kg) suggestive of partial diabetes insipidus (DI). A 24-hour urine collection had a volume of 9.2 liters. He had a normal hemoglobin A1c. Hormonal work-up was unremarkable with normal range his prolactin, IGF-1, and a.m. cortisol (19 mcg/dl). He was already on levothyroxine with normal thyroid function tests and negative thyroid antibodies. Water deprivation testing confirmed a diagnosis of central DI and he was started on desmopressin. Magnetic resonance imaging (MRI) of the pituitary demonstrated diffuse PST with T2 hyperintensity and loss of normal T1 hyperintensity (“bright spot”) of the posterior pituitary. Repeat imaging 3 months later showed progressive thickening. He underwent full body positron emission tomography-computerized tomography (PET-CT) which demonstrated increased metabolism of the pituitary stalk, but no other suspicious uptake in other areas. Chest X-ray, tuberculin screen, angiotensin converting enzyme, and calcium were all normal. Patient underwent transsphenoidal stalk biopsy. Pathology demonstrated fibrosis and chronic inflammation without malignancy but otherwise was nondiagnostic. Based on these findings, he was presumed to have neuroinfundibulitis and is being actively followed with MRIs and labs. Conclusion: Isolated PST is exceedingly rare, especially in adults. The differential diagnosis includes neoplastic (germinomas, lymphoma, metastatic disease), autoimmune, and infiltrative disease (sarcoidosis, histiocytosis). One review of 38 adult patients with central DI and PST showed that almost half had neuroinfundibulitis. Of those, 4 were treated with corticosteroids and 7 were not. All patients showed reduction or resolution of PST on subsequent MRIs indicating that resolution of thickening can be spontaneous without steroid use, and can be followed by MRI and with hormone replacement for deficiencies (1). Because of the rarity of isolated neuroinfundibulitis, it is important that neoplastic and systemic diseases be ruled out in all patients with PST, as in the case of our patient.1.Devuyst F, Kazakou P, Baleriaux D, Alexopoulou O, Burniat A, Salenave S, et al. Central diabetes insipidus and pituitary stalk thickening in adults: distinction of neoplastic from non-neoplastic lesions. European Journal of Endocrinology. 2020;183(1):95-105.

Occult Carcinoid Causes Cushing’s Syndrome

Introduction: Lung neuroendocrine tumors (NETs) are a common cause of ectopic ACTH-secretion. Only 3% of NETs cause Cushing’s syndrome1; the majority are small and may be radiographically occult. Additionally, the responses to dexamethasone, metyrapone, and oCRF can be indistinguishable from that observed in pituitary Cushing’s disease2. These challenges lead to misdiagnosis and unnecessary procedures. Case Description: 45-year-old male presented for resection of right-sided pulmonary carcinoid tumor. He was diagnosed with Cushing’s syndrome in 2011 when he experienced uncontrolled hypertension and excessive weight gain with elevations in cortisol and ACTH levels. He underwent transsphenoidal pituitary resection in May 2011 for a possible pituitary microadenoma. Post-operative worsening hypertension, weight gain, and striae led to bilateral adrenalectomy in November 2011, complicated by retroperitoneal hemorrhage and resuscitation-induced pulmonary edema. On chest CT in early 2012, an 8 mm incidental right pulmonary nodule was documented. 8 years later, chest imaging for mild COVID-19 infection again revealed a right-sided pulmonary nodule. He underwent CT-guided biopsy of the nodule in July 2020 with pathology demonstrating carcinoid histology. Right lower lobectomy was performed. Pre-operative ACTH was 1673 pg/mL (normal: 10-60 pg/mL) and post-operative ACTH was 16 pg/mL. The resected tumor stained positive for ACTH, confirming that carcinoid tumor was the source of Cushing’s for the past decade. Conclusion: The diagnosis of ectopic Cushing’s syndrome can be elusive, leading to surgeries with significant morbidity, as seen in our patient. In one retrospective review, 14% of patients with Cushing’s had transsphenoidal resection before they were diagnosed with an ectopic source3. Ectopic Cushing’s syndrome can be a challenging diagnosis to make and a multidisciplinary approach with close collaboration between endocrinologist, radiologist, surgeon and pathologist may increase the diagnosis accuracy. Citations: 1Kamp, K, Alwani, R A, Korpershoek, E, Franssen, G., de Herder, W W, & Feelders, R A. (2016). Prevalence and clinical features of the ectopic ACTH syndrome in patients with gastroenteropancreatic and thoracic neuroendocrine tumors, European Journal of Endocrinology, 174(3), 271-280. Retrieved Jan 15, 2021, from https://eje.bioscientifica.com/view/journals/eje/174/3/271.xml 2Malchoff CD, Orth DN, Abboud C, Carney JA, Pairolero PC, Carey RM. Ectopic ACTH syndrome caused by a bronchial carcinoid tumor responsive to dexamethasone, metyrapone, and corticotropin-releasing factor. The American Journal of Medicine. 1988;84(4):760-764. doi:10.1016/0002-9343(88)90116-7 3Ioannis Ilias, David J. Torpy, Karel Pacak, Nancy Mullen, Robert A. Wesley, Lynnette K. Nieman,Cushing’s Syndrome Due to Ectopic Corticotropin Secretion: Twenty Years’ Experience at theNational Institutes of Health, The Journal of Clinical Endocrinology & Metabolism, Volume 90, Issue8, 1 August 2005, Pages 4955–4962, https://doi.org/10.1210/jc.2004-2527

Strong correlation between prevalence of severe vitamin D deficiency and population mortality rate from COVID-19 in Europe.

BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a very wide range of disease severity: from completely asymptomatic to fatal, and the reasons for that are not well understood; however, there are some data that show vitamin D may have a protective effect.MethodsTo retrieve the vitamin D levels data, the authors analyzed the vitamin D European population data compiled by 2019 European Calcified Tissue Society (ECTS) statement on vitamin D status published in the European Journal of Endocrinology. For the data set to be used for analysis, only recently published data that included general adult population of both genders aged 40–65 years or wider and must have included the prevalence of vitamin D deficiency.ResultsThere were data sets from 10 countries that fitted the criteria and were analyzed. Severe vitamin D deficiency was defined as 25(OH)D less than 25 nmol/L (10 ng/dL). Pearson correlation analysis between death rate per million of population from coronavirus disease 2019 (COVID-19) and prevalence of severe vitamin D deficiency showed a strong correlation with r = 0.79, p = 0.007. Over time, correlation strengthened, and r coefficient asymptotically increased. After adjusting for countries’ age structure and per capita health expenditures, multiple linear regression analysis showed that higher prevalence of severe vitamin D deficiency is associated with increased mortality. Each 1% increase in prevalence increased deaths by 55 per million (95% confidence interval, CI 8–102), p = 0.03.ConclusionThe authors recommend universal screening for vitamin D deficiency, and further investigation of Vitamin D supplementation in randomized control studies, which may lead to possible treatment or prevention of COVID-19.

SAT-340 Familial Hypocalciuric Hypercalcemia Due to a C.571G>A (p.Glu191Lys) Variant in the GNA11 Gene

Background: Familial hypocalciuric hypercalcemia (FHH) type 1 is caused by inactivating pathogenic variants in the calcium sensing receptor (CASR) gene and clinically presents with serum hypercalcemia, low urine calcium excretion, and inappropriately normal PTH response. In a minority of patients with CASR-negative FHH (up to 26%), variants in AP2S1 are linked to FHH type 3. Similarly, inactivating pathogenic variants in the GNA11 gene have been shown to cause FHH type 2 in up to 10% of CASR and AP2S1 negative cases.1 Clinical case: A four-month old male presented to the ED for symptoms of polyphagia and polyuria. Biochemical evaluation found a serum calcium of 11.9 mg/dL (8.7-11.0 mg/dL), magnesium 2.4 mg/dL (1.6-2.3 mg/dL), 25-OH Vit D 38 ng/mL (30 -100 mg/dL) and intact PTH 27.8 pg/mL (15-65 pg/mL). His further labwork fit clinically with FHH with a urine calcium-creatinine ratio < 0.09 (<= 0.20), accompanied by a serum calcium level of 11.9 mg/dL and iCal of 1.48 mmol/L (1.13 – 1.37 mmol/L). Subsequent monitoring of serum calcium levels showed improvement with time, along with improvement in polyphagia and polyuria.Of note, mother also has a history of hypercalcemia that was diagnosed at age fifteen as part of a rheumatology evaluation. At diagnosis, her calcium was 12.1 mg/dL (9.3-10.6 mg/dL), Mg 2.3 mg/dL, phosphorous 3.3 mg/dL (2.3-4.8 mg/dL), intact PTH 39 pg/mL, and urine calcium-creatinine ratio of 0.04 (<= 0.20). She was treated with calcitonin, during which she developed hypercalciuria with elevated PTH of 88 pg/mL. A parathyroid uptake scan was concerning for adenomatous changes in the right upper parathyroid gland, but she was subsequently lost to follow-up without additional evaluation.Sequencing of the AP2S1, CASR, CDC73, CYP24A1, GCM2, GNA11, MEN1, PTH1R, or SLC34A1 genes by Next-generation sequencing methodology was completed in the patient and only revealed a maternally inherited missense variant of unknown significance of c.571G>A (p.Glu191Lys) in GNA11. This G to A transition in exon 4 substitutes a glutamic acid for a lysine at codon 191 of a highly conserved amino acid. This variant has not been previously reported in affected individuals nor has it been observed in the healthy population per the gnomAD population database. It is predicted to be deleterious/probably damaging by in silico tools (SIFT, PolyPhen2). Conclusion: To our knowledge, this is the first case demonstrating the presence of a c.571G>A (p.Glu191Lys) variant in the GNA11 gene, in a child with familial hypocalciuric hypercalcemia as well as in his affected mother. In cases with strong suspicion of FHH despite negative CASR and AP2S1 analyses, genetic analysis of GNA11 should also be considered.Reference:(1) Hovden, S., Rejnmark, L., Ladefoged, S., & Nissen, P. (2017). AP2S1 and GNA11 mutations – not a common cause of familial hypocalciuric hypercalcemia, European Journal of Endocrinology, 176(2), 177-185.

MON-451 An Unusual Case of Follicular Thyroid Cancer with Pulmonary Metastasis and Concurrent Hyperthyroidism

Introduction: Follicular Thyroid Cancer (FTC) accounts for approximately 12 % of all thyroid cancers and is the second most common cause of differentiated thyroid cancer. However, coexisting hyperthyroidism and thyroid malignancy is considered a rare event and is thought to have a prevalence of 0.21–9.0 %. We describe a compelling case of metastatic FTC initially presenting with subclinical hyperthyroidism progressing to overt hyperthyroidism.Clinical Case: An 88-year-old man with a history of prostate cancer, previous tobacco dependence, and hypertension initially presented with complaints of a chronic non-productive cough associated with unintentional weight loss and fatigue. Initial imaging included a chest CT that showed several bilateral pulmonary nodules suspicious for metastatic disease, as well as an enlarged left-sided thyroid mass, which extended from the inferior pole into the mediastinum. FDG PET/CT showed avid disease identified in the lung. CT-guided lung biopsy was performed, and histopathology revealed FTC. Thyroid function tests (TFTs) revealed a Tg level of 1427 (0.00–33.70), TgAb <1.0 (< 13.6), TSH 0.05 (0.40–4.50), FT4 1.1 (0.8–1.8) and FT3 3.4 (2.3–4.2). Biochemical testing was consistent with subclinical hyperthyroidism. Neck ultrasound showed bilateral thyroid nodules, the largest located on the left mid-pole measuring 3.4 x 3.2 x 3.7 cm. He underwent a whole-body I-131 diagnostic scan, which showed intense uptake of the radionuclide within the thyroid gland, more evident on the left, but additional metastatic lesions elsewhere in the visualized body were not possible. TFTs were repeated, which showed a TSH of 0.01, FT4 of 2.0, and FT3 of 6.4. He was subsequently started on methimazole daily and eventually became euthyroid. Due to advanced age, significant mediastinal extension, and lung metastasis, the patient was not a candidate for surgical resection and treatment with a targeted tyrosine kinase inhibitor. He ultimately opted for an observational approach.Conclusion: Although metastatic FTC carries a poor prognosis, concurrent hyperthyroidism is thought to be associated with a more aggressive disease course and higher mortality compared to differentiated thyroid cancers in euthyroid patients.Sources: 1. Pazaitou-Panayiotou, K., Perros, P., Boudina, M., Siardos, G., Drimonitis, A., Patakiouta, F., & Vainas, I. (2008). Mortality from thyroid cancer in patients with hyperthyroidism: the Theagenion Cancer Hospital experience, European Journal of Endocrinology, 159(6), 799–803.2. Benjamin Momo Kadia, Christian Akem Dimala, Ndemazie Nkafu Bechem, Desmond Aroke. BMC Res Notes. 2016; 9: 369.3. Parameswaran R, Shulin Hu J, Min En N, Tan WB, Yuan NK. Patterns of metastasis in follicular thyroid carcinoma and the difference between early and delayed presentation. Ann R Coll Surg Engl. 2017;99(2):151–154.

SAT-214 Steroid Induced Pheochromocytoma Crisis

BACKGROUND:The factors triggering adrenergic crisis in pheochromocytoma are most often related to induction during anesthesia or manipulation of tumor during surgery. A variety of drugs have also been reported to be associated with adrenergic crisis, however there are only scarce case reports on pheochromocytoma crisis induced by steroids. Here we present a case of steroid induced pheochromocytoma crisis.Clinical Case:58 year-old female with history controlled hypertension on Lisinopril 10 mg daily, presented to hospital with two day history of fatigue, shortness of breath, and abdominal pain. A CT chest and abdomen showed emphysema and an indeterminate right adrenal gland nodule. Due to patient symptoms and findings of emphysema patient was started on Prednisone 40 mg daily. Home Lisinopril was restarted and patient was placed on sodium restriction. Ten hours after the start of prednisone the patient developed sudden onset hypertension with BP >200/100 mmHg for which she was given labetalol intravenously. The patient developed orthostatic hypotension hours after with BP readings as low as 50s/40s. Due to labile BP a work-up for adrenal adenoma was started. Plasma and urine metanephrines and noremetanephrines returned 7–11 times and 4–15 times above upper limit of normal (ULN) respectively. Plasma and urine metanephrines were repeated when patient was off steroids and normotensive and still returned abnormally high (about 2–3 times ULN) along with elevated urine catecholamines (epinephrine 6.5 times ULN and with only a slight elevation in norephinephrine and normal dopamine levels). A dedicated adrenal scan showed a 2.2 cm right adrenal mass with homogeneous enhancement, 130 HU, with an absolute and relative washout of 65% and 44% respectively, not consistent with a benign adenoma. Patient was placed on a high salt diet along with fluids and doxasozin. Once appropriately alpha blocked, metoprolol was added prior to surgery.Clinical lessons:In the setting of labile BP, one should keep a high clinical suspicion for pheochromocytoma. Orthostatic hypotension here was related to epinephrine predominance pattern of secretion and volume depletion. Steroids should be avoided in patients with known pheochromocytoma or in those with an adrenal adenoma without a negative biochemical workup for a pheochromocytoma as it could precipitate an adrenergic crisis possibly by inducing catecholamine synthesis and release and sensitizing target organs to the effects of catecholamines.Reference:1. Rosas AL, et al. Pheochromocytoma crisis induced by glucocorticoids: a report of four cases and review of the literature. European Journal of Endocrinology (2008) 158 423–429.

SAT-313 Catecholamine-Induced Cardiomyopathy in Pheochromocytoma during Pregnancy

Introduction: This case illustrates an uncommon initial presentation of cardiomyopathy in a pregnant woman who was later found to have Pheochromocytoma. Case: A 33-year-old female who is 19 weeks pregnant with no significant past medical or family history presented to the hospital with pleuritic chest pain associated with palpitations and dyspnea. Echocardiogram showed mildly dilated left ventricle with mild global left ventricular (LV) systolic dysfunction and an ejection fraction (EF) of 40-50%. Electrocardiogram (EKG) showed Q waves, with peak troponin of 1.8. Her symptoms were attributed to a post-viral perimyocarditis, was treated symptomatically and discharged home. She presented again at 22 weeks of pregnancy due to the same symptoms. Repeat echocardiogram showed improvement of cardiac function with normal EF and LV function; hence, she was once again treated symptomatically and discharged to home. The rest of her pregnancy was unremarkable. She carried to term and had an uncomplicated vaginal delivery. One week postpartum she presented to the hospital this time with complaints of intermittent headaches, episodic palpitations and new onset hypertension with systolic blood pressure (BP) in the 170s (<130mmHg). Pre pregnancy and BP during pregnancy were within normal limits. Diagnostic testing for secondary causes of hypertension were done which were all negative except for plasma catecholamines: metanephrine 24 nmol/L (<.50), normetanephrine 8.3nmol/L (<.9), epinephrine >1354 pg/ml (<642), and norepinephrine 2669 pg/ml (<642). 24 hour urine results showed: metanephrine 20 600mcg/24hr (<400), normetanephrine 3540 mcg/24hr (<900), total metanephrines 24 140 mcg/24hr (<1300), epinephrine 583 mcg/24hr(<21), norepinephrine 645 mcg/24hr (15-80). CT of the abdomen showed a 7.9x7x8.2 cm right adrenal mass. She underwent a laparoscopic right adrenalectomy and histopathology confirms the diagnosis of Pheochromocytoma. Her symptoms resolved after surgery with BP returning to normal. Repeat plasma catecholamines post surgery also returned to normal limits. Discussion: Pheochromocytoma during pregnancy is an extremely rare event with a reported incidence of .007% with an antepartum diagnosis that is only made 75% of the time (Van der Weerd et al., 2017). It is most often found during the third trimester of pregnancy and patients are more symptomatic during this time due to the compression of the enlarging gravid uterus on the tumor causing catecholamine release. Diagnosis is difficult especially in this case because the patient did not initially present with the classic symptoms until postpartum. Reference: Weerd, K. V., Noord, C. V., Loeve, M., Knapen, M. F., Visser, W., Herder, W. W., Feelders, R. A. (2017). ENDOCRINOLOGY IN PREGNANCY: Pheochromocytoma in pregnancy: Case series and review of literature. European Journal of Endocrinology,177(2). doi:10.1530/eje-16-0920

SAT-465 Somatostatin Receptor Ligand as Initial Therapy in a Patient with Pituitary Microadenoma and Acromegaly: Temporary Remission and Recurrence

BACKGROUND: Transsphenoidal surgery is recommended as initial therapy for microadenomas causing acromegaly. Primary medical therapy with somatostatin analogues has shown to cause a reduction in the size of microadenomas and secretion of growth hormone. Normalization of IGF-1 levels with somatostatin receptor ligand does not occur in most patients treated with primary therapy. We present a case of acromegaly with microadenoma treated with somatostatin analogue showing complete resolution on MRI within 1 year of treatment. We show that after one year of treatment discontinuation, reappearance of microadenoma to original presentation and elevation of IGF-1 was noted. CLINICAL CASE: A 43-year woman presented with headaches, frontal bossing, jaw enlargement and galactorrhea. Initial tests revealed high prolactin 31.6 ng/ml (1.2- 29.9 ng/ml), elevated IGF-1 level of 233 ng/ml (68 – 225 ng/mL) and abnormal growth hormone suppression testing. Brain MRI showed a 4 mm microadenoma within the left side of the pituitary gland. She was referred for neurosurgery, which she declined. Subsequently, medical therapy was started with Cabergoline, resulting in normalization of prolactin14.2 ng/ml (1.2- 29.9 ng/ml). Somatostatin receptor ligand was initiated with lanreotide 90 mg monthly. After 1 year of treatment patient showed clinical improvement, normalized IGF-1 level 67ng/ml (68 – 225 ng/mL) and markedly reduced size of the microadenoma on brain MRI. Patient stopped the medication due to financial difficulties and within one year had a recurrence of symptoms including high IGF-1 of 331ng/ml (68 – 225 ng/mL) and reappearance of the microadenoma on brain MRI. CONCLUSION: Acromegaly is a rare and challenging disease to treat. Somatostatin receptor ligands are not recommended as primary therapy for microadenoma causing acromegaly, despite often needed as adjuvant treatment post-surgery. Medical therapy has been described for patients who do not undergo surgery but is generally not curative. Although we present great improvement in our patient with somatostatin treatment as primary therapy, remission was short lived, and patient will need surgical resection to achieve cure from her disease. Radiological recurrence after discontinuation of medical therapy has not been reported. Using somatostatin receptor ligands as initial therapy for cure of acromegaly offers benefit as demonstrated in our case, but long term remission needs to be evaluated over a longer treatment period. References Ramírez, C., Vargas, G., González, B., Grossman, A., Rábago, J., Sosa, E., Mercado, M. (2012, 1). Discontinuation of octreotide LAR after long term, successful treatment of patients with acromegaly: is it worth trying? European journal of endocrinology, 166(1), 21-26. doi:10.1530/EJE-11-0738

The relationship between serum IGF-1, handgrip strength, physical performance and falls in elderly men and women

InAugust 2018, in the volume 179, issue 2 of the European Journal ofEndocrinology van Nieuwpoort et al. (1) addressed the role of IGF-1on muscle function and clinical implications of this relationship, i.e., interm of risk of falls, in community dwelling elderly.

Developing a pituitary distress thermometer (PDT) - a means to improve patient quality of life

Conclusions 1.Sollner W, DeVries A, Steixner E, Lukas P, Sprinzl G, Rumpold G & Maislinger S (2001) How successful are oncologists in identifying patient distress, perceived social support, and the need for psychosocial counselling? British Journal of Cancer, 84(2): 179-185 2.Sonino N, Ruini C, Navarrini C et al. Psychological Impairment in patients treated for pituitary disease: a controlled study. Clinical Endocrinology. 2007; 67(5): 719-26. 3.Webb S, Prieto L, Badia X et al. Acromegaly quality of life questionnaire (AcroQoL) a new health-related quality of life questionnaire for patients with acromegaly: development and psychometric properties. Clinical Endocrinology. 2002; 57(2): 251-8. 4.Webb S, Badia X & Surinach N. Validity and clinical applicability of the acromegaly quality of life questionnaire, AcroQoL: a 6-month prospective study. European Journal of Endocrinology. 2006; 155(2): 269-77. 5.Webb S, Badia X, Barahona M et al. Evaluation of health-related quality of life in patients with Cushing's syndrome with a new questionnaire. European Journal of Endocrinology. 2008; 158(5): 623-30. 6.Lovas K, Curran S, Oksnes M et al. Development of a disease-specific quality of life questionnaire in Addison’s disease. Journal of Clinical Endocrinology and Metabolism. 2009; 95(2): 545-51. Pituitary tumours, though almost always benign, are now included with other central nervous system tumours in cancer services. It therefore seems appropriate to adapt this oncology tool for use with pituitary patients. • Research has shown that high levels of patient distress may not be identified during consultations with healthcare professionals (HCPs), resulting in significant patient dissatisfaction with care and additional use of primary and secondary care services[1].

PMM.37 Undiagnosed Pheochromocytoma in Labour – Would you suspect it?

Aims/ObjectivesThis is a case presentation aiming to draw attention to the clinical suspicious of pheochromocytoma as a differential of severe hypertension in labour.BackgroundPheochromocytoma in a pregnant woman is extremely rare...

Toxicity beyond the Lung: Connecting PM 2.5 , Inflammation, and Diabetes

Exposure to fine particulate matter (PM2.5) has been associated with increased risk of heart disease,1 insulin resistance (IR),2 and diabetes,3 all conditions that are characterized by inflammation.4 Experimental data suggest a high-fat diet2 may exacerbate the health effects of inhaled PM2.5; obese people also appear to be at increased risk.1 In this issue of EHP, investigators tease out some of the complex cellular mechanisms that could explain how PM2.5 may work with a high-fat diet to cause IR.5 Some of the authors previously reported that mice breathing PM2.5 and eating a high-fat diet developed IR, systemic inflammation, and increased abdominal fat, compared with mice eating the same diet but breathing filtered air.2 For the current study, the investigators focused on CCR2, a protein that recruits innate immune cells to insulin-sensitive tissues such as visceral fat and the liver, where it induces the inflammation characteristically seen in animal models of obesity and type 2 diabetes.6 They compared wild-type mice that produce CCR2 with “knockout” (CCR2–/–) mice that don’t. All the mice were fed a high-fat diet and then for 17 weeks were exposed to either filtered air or air containing 117 µg/m3 of PM2.5. Among the key findings, PM2.5 exposure was associated with increased IR and increased levels of liver lipids in the wild-type mice. The elevated liver lipids resulted from a rise in SREBP-1c activity5; this protein helps regulate fatty acid synthesis.7 In contrast, liver lipid levels and SREBP-1c activity in CCR2–/– mice were equivalent whether the mice were exposed to PM2.5 or breathing filtered air.5 IR is also characterized by abnormal insulin signaling through the AKT pathway. Reduced phosphorylation of this enzyme is associated with inflammation.8 The researchers found that phosphorylation of AKT was reduced in wild-type mice exposed to PM2.5 but unchanged in CCR2–/– mice. PM2.5 exposure also was associated with higher levels of inflammatory F4/80 macrophages in visceral fat stores, but only in wild-type mice.5 The important message in all these findings is that PM2.5 recruits inflammatory cells via CCR2-dependent mechanisms. “This mechanism directly ties a known inflammatory mechanism in the pathogenesis of type 2 diabetes to exposure to environmental air pollution,” says study leader Sanjay Rajagopalan, division head for cardiology at the University of Maryland Medical Center. The protein CCR2 is involved in the inflammation that characterizes animal models of obesity and type 2 diabetes. Rajagopalan says the inflammatory damage likely creates a vicious cycle that can also contribute to cardiovascular disease and obesity. “We should look more closely at these kinds of associations in human epidemiological studies,” he says. PM2.5 is generated by vehicle exhaust, burning wood and coal, and industrial processes.9 Annual PM2.5 levels in cities in China, India, and Latin America can average 100–150 µg/m3, comparable to the PM2.5 exposure in this study.2 “It’s long been suspected that the immune system played a major role in ‘carrying’ the toxicity of air pollutants beyond the lung,” says Matthew Campen, an associate professor at the University of New Mexico College of Pharmacy, who was not involved in the study. The results by Rajagopalan’s team strongly support the role of the innate immune system in mediating PM2.5 toxicity in tissues far from the lung. The results, Campen says, also suggest that PM2.5 pollution could worsen cardiometabolic syndromes brought on by an unhealthy diet and lifestyle. “This public health burden may be offset by anti-inflammatory drugs or healthy diets,” he says. Alternatively, Rajagopalan proposes, “A practical solution would be to lower levels of PM2.5.” As Campen wryly points out, “These differing approaches may reflect the backgrounds of an environmental health scientist who understands the challenges entailed in further reductions in air pollution levels, compared with a cardiologist who understands how difficult it is to change human behavior.”

Current Resources for Evidence‐Based Practice January/February 2013

Current Resources for Evidence‐Based Practice January/February 2013

Medullary Thyroid Carcinoma: Who's on First?

ThyroidVol. 22, No. 5 Editorials and CommentaryMedullary Thyroid Carcinoma: Who's on First?Mimi I. Hu and Gilbert J. CoteMimi I. HuSearch for more papers by this author and Gilbert J. CoteSearch for more papers by this authorPublished Online:30 Apr 2012https://doi.org/10.1089/thy.2012.2205.edAboutSectionsView articleView Full TextPDF/EPUB ToolsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View articleFiguresReferencesRelatedDetailsCited bySmall-molecule inhibitors, immune checkpoint inhibitors, and more: FDA-approved novel therapeutic drugs for solid tumors from 1991 to 20218 October 2022 | Journal of Hematology & Oncology, Vol. 15, No. 1Hereditary and familial thyroid tumours14 December 2017 | Histopathology, Vol. 72, No. 1Noncoding RNA blockade of autophagy is therapeutic in medullary thyroid cancer8 December 2014 | Cancer Medicine, Vol. 4, No. 2Smoldering medullary thyroid carcinoma liver metastasis 37 years after resection of an organ-confined tumor18 February 2014 | Diagnostic Cytopathology, Vol. 43, No. 1Thyroid C-Cell Biology and Oncogenic Transformation23 October 2015Polymorphisms of cell cycle control genes influence the development of sporadic medullary thyroid carcinoma6 November 2014 | European Journal of Endocrinology, Vol. 171, No. 6Molecular Testing in Thyroid CancerThe Role of Cdk5 in Neuroendocrine Thyroid CancerCancer Cell, Vol. 24, No. 4Exomic Sequencing of Medullary Thyroid Cancer Reveals Dominant and Mutually Exclusive Oncogenic Mutations in RET and RASThe Journal of Clinical Endocrinology & Metabolism, Vol. 98, No. 2 Volume 22Issue 5May 2012 InformationCopyright 2012, Mary Ann Liebert, Inc.To cite this article:Mimi I. Hu and Gilbert J. Cote.Medullary Thyroid Carcinoma: Who's on First?.Thyroid.May 2012.451-453.http://doi.org/10.1089/thy.2012.2205.edPublished in Volume: 22 Issue 5: April 30, 2012PDF download

A critical review and meta-analysis of the association between overt hyperthyroidism and mortality

The authors and the journal apologise for an error in Figure 2 of this article published in European Journal of Endocrinology (2011) 165 491–497.

Is there a link between hypogonadism and vitamin D deficiency in aging men?

Secondary hypgonadism and compensated hypogonadism are associated with vitamin D deficiency, according to a recent report in the European Journal of Endocrinology.

A prospective study of sex steroids, sex hormone-binding globulin, and non-vertebral fractures in women and men: the Tromsø Study

The authors apologise for errors in the results reported in their above titled article published in the European Journal of Endocrinology 2007 157 119–125.Due to a technical error, a number of fractures were not included in the database. In the cohort of 2750 participants, a total of 487 suffered a non-vertebral fracture (not 386 as stated in the article), and the incidence was 30.0 in women and 11.8 in men per 1000 person-years, respectively.The main results were unchanged after re-analysis and no significant association was present between sex steroids and risk of non-vertebral fractures after adjustment for age in both sexes. Each 1 S.D. higher SHBG increased the risk of non-vertebral fracture by about 20% in women (HR 1.15; 95% CI 1.03–1.29) and men (HR 1.18; 95% CI 0.99–1.41) after adjustment for age, height, weight, smoking and physical activity. After adjustment for BMD, the increased risk was attenuated and no longer statistical significant in women (HR 1.07; 95% CI 0.96–1.21) and men (HR 1.12; 95% CI 0.94–1.34) respectively.