bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detection of Sex Steroid Expressions in Benign Versus Malignant Adrenal Tumor Tissue Homogenates With Western Blot Analysis
Authors: Oguz Seda Hanife , Gunaydin Gurcan , Emre Gedik , Sokmensuer Cenk , Dagdelen Selcuk 
Published: May 2021

Abstract
Background: Adrenocortical cancer (ACC) is a rare tumor with poor prognosis. The prognostic value of sex steroid expressions in ACC, was firstly shown by our group with immunohistochemistry staining in paraffin embedded blocks (1). Aim: To detect the presence of sex steroid expressions in different types of adrenal fresh tissue samples by Western Blot method. Method: Adrenal fresh tissue samples were isolated from benign (patient 1: adrenal hemangioma, n: 1 intratumoral + 1 extratumoral tissue samples) and malignant tumors (patient 2: ACC, n: 4 intratumoral tissue samples). Expressions of estrogen receptor alpha (Erα), progesterone receptor A (PR), androgen receptor (AR) and aromatase proteins were investigated using Western Blot method in the tissue lysates obtained. Monoclonal antibodies that recognize a single determinant of the obtained denatured proteins with high affinity and specificity were used. GAPDH was used as control protein. After the primary antibody incubation, the incubation phase was started with the secondary antibody produced against the organism in which HRP (Horseradish Peroxidase) conjugated primary antibody was produced in order to visualize the primary antibody. ECL (Enhanced chemiluminescence) solution containing luminol, which is the substrate of the peroxidase enzyme contained in HRP conjugated to the secondary antibody, was used to enable the proteins to which the secondary antibody was bound to emit chemoluminescence. Finally, the densitometric densities of the bands obtained by chemiluminescence imaging were determined. Results: Expression of ER, AR, PR and aromatase was demonstrated in fresh tissue samples obtained from ACC, adrenal hemangioma and normal adrenal cortex. PR expression was higher in ACC lysates. ER and AR expressions were higher in hemangioma and normal adrenal cortex, respectively. Aromatase expression was also higher in adrenal hemangioma while similar in cancerous and normal adrenal tissue samples. Conclusions: We have demonstrated the dissimilarities between the expressions of sex steroid receptors and aromatase by using Western Blot method in fresh tissue samples obtained from different types of adrenal masses, including ACC. It would be possible to develop an in vitro experimental ACC model that can test the effect of sex steroid receptor ligands on tumor growth in order to clarify their role in adrenal tumorigenesis. Reference:1. Oguz SH, Sokmensuer C, Bayraktar M, Dagdelen S. Estrogen, progesterone, and androgen receptor expressions predict the prognosis for adrenocortical carcinoma. Endocrine Society’s Annual Meeting, 23–26 March 2019, New Orleans - USA. Journal of the Endocrine Society, Volume 3, Issue Supplement_1, April-May 2019, SUN-352.
Ectopic Adrenal Tumor in a Patient With Untreated Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency
Authors: Alba Eva L , Patel Kruti K , Levine Alice C 
Published: May 2021

Abstract
Case Presentation: A 43 year-old female was diagnosed at birth with non-salt wasting congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency and underwent clitoral reduction surgery. She was treated with hydrocortisone and had menarche at age 7 with irregular and heavy menses. At age 15 she had a D&C with removal of “something in her ovaries.” She stopped hydrocortisone at age 30 except for stress doses during illness. At age 35 she stopped oral contraceptives and thereafter has been amenorrheic. She presented with abdominal distention and constipation. On exam she had short stature, marked frontal and temporal balding, hirsutism, increased musculature and a large distended abdomen. Labs showed AM cortisol 3.1 mcg/dL (nl 10–20), ACTH 440 pg/ml (nl &lt;46), 17-OH Progesterone 11000 ng/dL (nl &lt;206), DHEAS 362 mcg/dl (nl &lt;430), FSH 0.2 mIU/ml, LH 2.7 mIU/ml, testosterone 618 ng/dl (nl 10–75), and estradiol 162 pg/ml (nl post menopause &lt;41). MRI showed a massive fibroid (30 cm), bilateral adrenal hyperplasia and a left paraaortic, retroperitoneal mass (5.9 cm). She underwent hysterectomy with removal of a 9.5 kg uterus containing degenerated fibroids, left adrenalectomy and removal of the left paraaortic mass that was initially read as oncocytic adrenal cortical neoplasm, metastatic. A similar oncocytic neoplasm was noted in the left adrenal gland and on further review with pathology the revised report read paraaortic mass, probable adrenal rest tumor.
Discussion: Excess androgens and chronically elevated ACTH levels in untreated CAH can lead to adverse effects beyond adrenal insufficiency and virilization. We present a woman with untreated classic CAH who developed a large fibroid and paraaortic adrenal cortical tumor. Fibroids have been described in CAH patients, a potential consequence of elevated androgens that are converted by aromatase in the endometrium to estrogens driving growth of fibroid tumors. Chronic ACTH can further act as a growth factor, leading to adrenal hyperplasia, adrenal tumors and ectopic adrenal rest tissue. Intra-adrenal tumors in untreated CAH are generally benign with rare cases of adrenal cortical carcinoma reported.
Ectopic adrenal rest tissue in untreated CAH is most commonly reported in testes. There have been rare case reports of ectopic adrenal rest tumors in the adnexa, broad ligament, and perirenal area. Our patient presents as an unusual case of ectopic adrenal rest tumor in the paraaortic region. Based on the atypical location and incomplete history available to the pathologist, it was initially read as metastatic adrenocortical carcinoma. Upon further review given the clinical information, the diagnosis was revised to indicate a pararenal adrenal rest tumor. This case highlights the importance of glucocorticoid compliance in CAH and the necessity to provide a clinical context for the pathologist in cases of extra-adrenal tumors in untreated CAH.
Excellent Maternal and Fetal Outcomes Associated With Early Detection and Treatment of Cushing’s Syndrome During Pregnancy
Authors: Wang Ally W , Xie Yan Yan Sally , Cheesman Khadeen C 
Published: May 2021

Abstract
Background: Despite its relative high prevalence in women of reproductive age, pregnancy is uncommon in Cushing’s syndrome (CS) as hypercortisolism typically results in anovulation and infertility. Early diagnosis and treatment are essential to reduce maternal and fetal complications.
Clinical Case: A 31-year-old woman with Type 2 diabetes mellitus and hypertension was referred for significantly elevated midnight salivary and urine cortisol levels consistent with CS. Six months after initial laboratory findings, she presented to our endocrinology clinic eight weeks pregnant with di/di twins. She reported worsening blood pressure and glucose control, mood fluctuations, and easy bruising for the past several months. Menses were regular prior to conception. Physical exam was notable for round facies, mild dorsal hump, and supraclavicular fullness. Lab tests at eight and thirteen weeks gestation respectively showed: elevated 24-hr urine free cortisol 368.5 and 597.5 ug/24hr (&lt; 45); elevated midnight salivary cortisol 0.88 mcg/dL (&lt;0.09) at eight weeks; ACTH &lt;1.1 and 8.1 pg/mL (7.2 - 63.3); and elevated morning cortisol 34.2 and 36 ug/dL (6.2 - 19.4). Her hemoglobin A1C was 8.1% on metformin and Levemir. Pituitary MRI was normal. MRI of the abdomen without contrast demonstrated a 2.5 x 3.5 cm solid homogeneous mass in the right adrenal gland. The patient underwent successful right adrenalectomy at seventeen weeks gestation and was discharged on glucocorticoid replacement. Glucose control was labile due to non-compliance but otherwise the remainder of her pregnancy was uncomplicated. The patient delivered healthy twins at thirty-five weeks. At six months postpartum she is doing well on low dose hydrocortisone replacement. Most recent hemoglobin A1C was 5.7% without diabetes medication.
Conclusion: There is no consensus on the management of CS during pregnancy due to the rarity of this condition. CS in pregnancy is associated with high maternal and fetal morbidity and mortality, thus early diagnosis and prompt treatment is essential. Our case demonstrates the importance of discussing contraception with Cushing’s patients of reproductive age. It also adds to prior studies and showed that when treated early in pregnancy, either surgically or medically, maternal and fetal risks such as uncontrolled diabetes and fetal loss are significantly reduced. The ideal management of these patients is an area of ongoing investigation.
Familial Adenomatous Polyposis Associated With Bilateral Adrenocortical Tumors and Agressive Desmoid Tumor
Authors: Neiva Raíssa P , Santos Larissa C O , Ledesma Felipe L , Feher Olavo , Srougi Victor , Tanno Fabio , Almeida Madson Q , Chambo Jose Luis , Mendonca Berenice Bilharinho , Fragoso Maria Candida 
Published: May 2021

Abstract
Background: Familial adenomatous polyposis (FAP) is an autosomal dominant condition caused by germline mutation in the tumor suppressor gene APC. FAP occurs in 1 to 10.000 individuals, and is characterized by hundreds to thousands of colonic adenomatous polyps with a high risk of developing into colorectal cancer. Extracolonic manifestations can be malignant or benign. The major causes of morbidity and mortality in patients with FAP are abdominal desmoid tumors, with incidences ranging between 7% and 17%. Adrenal incidentaloma are frequently discovered in these patients, generally as benign lesions when they undergo abdominal CT-scan in the course of surveillance. Adrenal lesions in FAP ranged from 7.4% to 16%. We described an unusual patient with FAP, associated with autonomous cortisol production due to bilateral adrenal tumors and the development of aggressive desmoid tumor after unilateral adrenalectomy. Clinical Case: A 33-years-old female FAP-patient presented with abdominal pain, weight gain (10kgs), humor instability, paroxysmal of chest pain, dizziness and tremors. The abdominal MRI showed a heterogeneous, left adrenal mass (9.0 x 7.9 x 6.7cm), suspected for malignant tumor, and right adrenal mass with 3.6 x 1.8 cm suggestive of adenoma. Abdominal CT and PETCTFDG revealed on the left adrenal lesion with 33UH and maxSUV 3.9 and a right adrenal lesion 13UH and maxSUV 3.1. Serum hormone levels were as follows: cortisol after DST (1mg-dexamethasone) 4.8 ug/Dl, ACTH 8,8pg/Ml with no other abnormal hormone secretion detected. Patient underwent left adrenalectomy. Histological analysis revealed Weiss 1, modified Weiss 2 and Ki67 &lt;1% compatible with adenoma. On follow-up, abdominal MRI revealed a 4.3cm-solid-homogeneous mass at the surgical incision, suspected of malignance. The mass progressively enlarged to 6.3 cm in diameter. Histological analysis of the biopsy identified a desmoid tumor. The contralateral adrenal tumor maintained stable during the follow-up; however, it began to produce cortisol autonomous secretion as observed on DST. The patient developed metabolic syndrome and did not present classical Cushing’ syndrome. Contralateral adrenalectomy was contraindicated because of concern of emergence of a new desmoid tumor. Discussion: FAP-associated with adrenal tumors can produce mineralocorticoids, corticosteroids, or both. Although adrenal cortical tumors have been reported frequently in FAP patients, the presence of bilateral commitment tumors on adrenal glands is extremely rare. Conclusion: We reported a woman with FAP and bilateral adrenal tumors with non-synchronic cortisol secretion associated with an aggressive desmoid tumor developing after the adrenalectomy. The patient is taking an adrenal inhibitor of steroidogenesis to control cortisol secretion and to provide clinical improvement.
Hyperaldosteronism in a Patient With Gastrointestinal Potassium Wasting
Authors: Amankwah Samuel , Fein Henry G 
Published: May 2021

Abstract
Background: Medical conditions causing hypokalemia can be masked by a diet very rich in potassium. The following case presents a patient who developed new onset symptoms of hypokalemia after immigrating to the United States. Clinical Case: A 35 year old man, native of Mali, had a history of intermittent muscle spasms and serum potassium of 3.0 mmol/L first recognized elsewhere in 2019. He was not on any home medications. He was admitted with postprandial generalized abdominal pain, diarrhea, and bright blood in his stools. Serum potassium was 2.7 (nl 3.5–5.1mmol/L). He required at least 120 mEq of intravenous and oral potassium chloride per day while hospitalized to achieve and maintain serum potassium in the normal range. Colonoscopy found segmental colitis and it was thought that his hypokalemia was due to gastrointestinal losses. However, studies demonstrated urinary potassium wasting. A 1.9 cm nodular mass of the left adrenal gland was found on CT of the abdomen, and the differential diagnosis was expanded to include hypokalemia secondary to primary hyperaldosteronism or renal tubulopathies such as Bartter and Gitleman syndromes. The patient was normotensive and had biochemical findings that were consistent with Bartter syndrome including metabolic alkalosis, hypercalciuria, elevated urine sodium and chloride, and normal serum magnesium levels. However, he had low plasma rennin activity with an elevated serum aldosterone on three tests over two months (the last test was more than one month after normalization of bowel function). On all of these, the aldosterone to renin ratio was greater than 20 ng/mL/hour. The persistent suppression of plasma rennin with elevated aldosterone in the setting of left adrenal mass narrowed the differential diagnosis to primary hyperaldosteronism, as elevated rennin would be expected in Bartter syndrome. Since discharge, he has received 80 meq of daily oral potassium in divided doses, which has kept serum potassium at or below the lower limit of normal. Further management will consist of either pharmacologic or surgical treatment with or without adrenal venous sampling. Conclusion: The patient had hypokalemia for which an endocrine etiology could have been easily overlooked and attributed to gastrointestinal losses. This case demonstrates the very close clinical similarities between primary hyperaldosteronism and renal tubulopathies. However, there are biochemical patterns that can be relied on to help differentiate amongst these disorders. This patient with primary hyperaldosteronism may not have been hypokalemic in his native country due to consuming a diet rich in potassium.
Hyperkalemic Paralysis Due to Addison’s Disease
Authors: Chiwome Lawman , Yidana Daniel , Mung Sai Man 
Published: May 2021

Abstract
A 60-year-old woman with type 1 diabetes mellitus, past history of breast cancer, degenerative disc disease, hypothyroidism and asthma gave a 5-day history of flaccid paralysis and a 5-month history of back pain and worsening mobility. Investigations revealed hypercalcemia, hyperkalemia and hyponatremia which were initially thought to be due to hypercalcemia of malignancy on the assumption that her breast cancer had recurred. Imaging of the spine did not reveal cauda equina syndrome. There was no clinical and biochemical improvement in spite of fluid resuscitation.
Hypoadrenalism was suspected and confirmed three days later. Adrenal replacement therapy fully resolved her paralysis within 24 hours.
Addison’s disease is a rare clinical entity that requires a high index of suspicion. It may rarely present with weakness and/or back pain. Early recognition and treatment of Addison’s disease adequately resolves hyperkalemic paralysis. It is good clinical practice to keep an open-ended differential list to help reduce diagnostic suspicion bias.
Iatrogenic Cushing Syndrome and Secondary Adrenal Insufficiency Due to an Interaction Between Fluticasone and Ritonavir
Authors: Gutiérrez Lorena Suárez 
Published: May 2021

Abstract
Introduction: The interaction between corticosteroids and protease inhibitors (PIs) is a clearly described drug interaction. Several case series have been described.-Fluticasone is the one with the greatest potential risk of producing iatrogenic adrenal insufficiency given its pharmacokinetic characteristics.
Clinical Case: 44-year-old woman diagnosed with HIV (human immunodeficiency virus) category B3 diagnosed in 1989; multiple antiretroviral treatments. Severe lipodystrophy Also HCV genotype IA. Bronchial asthma since 2000. A treatment with fluticasone 1 inh / 24h, salbutamol on demand, darunavir 800 mg / day and ritonavir 100 mg / day. He had known lipodystrophy since 2001 and the abdominal perimeter was controlled, showing an increase in it. Likewise, she presented progressive proximal weakness in the lower limbs, with increased hair, capillary fragility and alopecia, which is why she was referred to Endocrinology. Moderate hirsutism, muscle atrophy were observed and in the analytical study: normal FSH and LH. Testosterone 0.05 ng / ml (0.1–0.9), ACTH 1.0 pg / ml (7.2–63.3), Cortisol am 0.65 µg / dl (4.30–22.40). Urinary free cortisol 3.74 µg / 24h (36–137). A Synacten Test is performed: Basal 0.52; 30 min 2.33; 60 min 2.84 with ACTH 1 and a diagnosis of iatrogenic independent ACTH Cushing Syndrome associated with secondary adrenal insufficiency.
With this diagnosis, he was referred to the pulmonology clinic for a change from inhaled corticosteroid to beclomethasone and replacement treatment with hydroaltenesone was started. Three months later, he was admitted for a fever after stopping hydroaltesone. It was restarted, antibiotic treatment was prescribed, and she was discharged home with a new regimen of antiretrovirals (raltegravir, tenofovir, and abacavir).
Clinical Lesson: Fluticasone is a synthetic steroid that is cleared by the cytochrome P450 enzyme CYP3A4, which is inhibited or enhanced by a multitude of drugs, including ritonavir. As it is not metabolized, there is an increase in circulating levels, causing a decrease in ACTH secretion and therefore a suppression of the adrenal gland with its insufficiency and cushing syndrome. In our case and usually, the initial signs are difficult to detect due to their overlap with lipodystrophy associated with protease inhibitors. Although there is no agreement in the literature: the options are the replacement of fluticasone with another corticosteroid that is not a CYP3A4 substrate such as beclomethasone and the replacement of ritonavir with another antiretroviral (as in our case) or the reduction of the dose of fluticasone. It is recommended to avoid the initiation of fluticasone in patients receiving ritonavir. Substitution treatment with a progressive reduction in dose is performed with hydroaltesona. Most cases resolve in 9–12 months.
Immune Check Point Inhibitors Triggering Non Autoimmune Polyendocrinopathy
Authors: Vergne-Santiago Norma , Sola Sanchez Ernesto Jos E , Garcia Michelle Marie Mangual 
Published: May 2021

Abstract
The superlative therapeutic response of cancer immunotherapy is activation of the immune system against cancer cells. Currently, one of the most considered immune system enhancer are the immunomodulatory antibodies well known as checkpoint inhibitor therapy. Among this type of treatment, programed cell death-1 receptor blocker, is one of the most sought-after therapies on demand now a day. Notwithstanding the important clinical benefits of this therapeutic modality, serial autoimmune adverse effects and variety of atypical presentations of life-threatening endocrinopathies are expected to occur.
We present a case of a 78-year-old man with dyslipidemia and lung CA who was referred to our clinic after developing electrolyte disturbances with associated dizziness and fatigue one month after Pembrolizumab therapy initiation. Physical exam was unremarkable. Laboratory data was consistent with mild hyponatremia, hyperkalemia and adequate fasting blood sugar levels. Aldosterone levels were extremely low, ACTH levels were extremely high with inappropriate low total cortisol response and negative 21-Hydroxylase antibodies. Diagnosis of primary adrenal insufficiency was established and Fludrocortisone 0.05 mg PO daily therapy was started with further resolution of hyponatremia and initial symptoms. In addition, concurrent primary hyperthyroidism along with thyroid RAIU-Scan results were consistent with thyroiditis, but TSI and TPO’s antibody levels were unexpectedly negative. Eventually, a suspicious thyroid nodule was identified requiring biopsy. Initial FNA results showed a follicular lesion of undetermined significance followed by a benign finding when repeated after six months. During follow up, patient’s primary hyperthyroidism converted to severe primary hypothyroidism without any intervention for her prior hyperthyroidism. Patient’s TPO’s levels remain undetectable and his current status is post-thyroiditis with residual primary hypothyroidism. Primary adrenal insufficiency also persist and its antibodies have not yet been identified either.
It is known that autoimmunity can predispose to the development of primary adrenal and thyroid disorders in patients undergoing PD-1 receptor blockers therapy against cancer. Both disorders are increasingly recognized and reported as one of the most common adverse effects presenting in patients treated with these agents. However, to our knowledge, cases of non-immune related adverse effects are barely documented. This case of uncommon endocrine manifestations related to checkpoint inhibitors therapy is meritorious of being reported since it should raise awareness in the medical community for prompt identification of signs and symptoms, as well as to offer adequate management, accurate treatment and provide a better standard of care.