bluuebunny/crossref_metadata_2025 huggingface dataset:
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

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 <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

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

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

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

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.
Incidental Giant Cystic Phaeochromocytoma: A Case Report
Authors: Dultra Bastos Gabriel Fernando , Falcão Camila Kruchewsky , Lins Rolim Maria Creusa de Albuquerque
Published: May 2021

Background: This case report describes a large sporadic benign phaeochromocytoma with classic symptoms and an unexpected SARS-CoV-2 virus contagious during the first pandemic wave. Clinical Case: A 61-years-old healthy man was admitted in the hospital emergency with hypertension, facial flushing, headache, nausea, vomiting and tremors. The patient presented hypertensive encephalopathy requiring orotracheal intubation. During the procedure, after rocuronium administration, the arterial pressure levels suddenly incresead more. An abdomen CT performed for vomiting investigation showed a mass in the left upper quadrant measuring 12.3 x 8.1 x 11.4 cm, central cystic area and sparse coarse calcifications, solid component density of 30 UH in the non-contrast phase and absolut washout of 48%, suggesting phaeochromocytoma (FEO) etiology. The patient renal function impaired and hemodialysis was required as replacement therapy. Even with small amount of urine available for exams, 24h urine tests were compatible with FEO diagnosis: (normetanephrines above 4260 mcg/L, n< 732 mcg/L, 250 mL of urine). Considering the severity of symptoms, a chest CT scan was provided, not demonstrating any metastatic disease. Parenteral antihypertensive medication to manage blood pressure was required and this withdraw was reached after the introduction of prazosin 2 mg twice a day. After adequate preoperative preparation, the surgical removal was performed. Systolic BP intraoperative fluctuations occurred, with variations between 70 and 210mmHg. Splenectomy was necessary due the intimate contact with the adrenal mass. No obvious metastases were observed. The anatomopathological showed a 390 grams adrenal mass confirming FEO (PASS score 5). Genetic panel for phaeochromocytoma and paraganglioma with complete sequencing found no pathogenic variants in any of the 22 genes analyzed, suggesting sporadic etiology. The patient got infected with COVID-19 after a family visitor confirmed by molecular test. He developed mild respiratory symptoms, delaying his hospital discharge. He was released seven weeks after surgery with complete kidney recover function using low doses of prazosin. Plasma metanephrines and normetanephrines were normal. Conclusion: Phaeochromocytoma is a rare disease with no specific clinical signs and symptoms. It implies in potentially lethal cardiovascular complications, especially during the COVID-19 pandemic. On the other hand it is a curable illness through the surgical tumor removal. Attention should be paid to high blood pressure levels even after the tumor is removed which can be justified by the remaining vascular hypertrophy as long as the suspicion of malignant FEO is excluded.
Incidental Pheochromocytoma: Silent but Violent
Authors: Bantu Sravani , Vallepu Shirisha R , Gunda Mouna , Thudi Vaishali
Published: May 2021

Background: Pheochromocytoma is a rare catecholamine secreting neuroendocrine tumor. It arises from the chromaffin cells of adrenal medulla. It is diagnosed in 5–6.5% of adrenal incidentalomas which is not common. The usual clinical presentation includes the classic triad of sweating, headache and tachycardia. However, asymptomatic cases are seen in 8% of the patients with pheochromocytoma. We present a clinically asymptomatic patient diagnosed during work up of adrenal incidentaloma. The possible etiology for silent presentation includes one of the following:(i) Presence of a smaller functional tissue (ii)Accelerated turnover of the tumor causing release of the unmetabolized catecholamines in small amounts (iii) Pulsatile tumor secretion (iv)Tumors triggered by stress (v) Laboratory errors due to inappropriate handling of specimen at high-temperature (vi) False negative test results secondary to caffeine ingestion in the prior 24 hours.

Clinical Case: 59 years old Caucasian female with past medical history of type 2 diabetes mellitus, obesity, essential hypertension, nonischemic cardiomyopathy, and asthma presented to the emergency room with complaints of worsening shortness of breath and pedal edema for 1 month. Physical exam: Blood pressure 146/78 mm of Hg and heart rate 82 beats/min, mild pedal edema, no pulmonary crackles. On imaging, CT angio chest showed irregularly enhancing right adrenal mass measuring 3.4 cm. This adrenal incidentaloma was not visualized on imaging done 5 years ago. Further, MRI abdomen revealed 4.1 cm right adrenal mass. Laboratory testing showed high total plasma

metanephrines: 890 pg/ml (< or = 205), 24-hour urine metanephrines: 2337 (140–785), A1C: 10%. This confirmed the diagnosis of adrenal pheochromocytoma. Preoperatively, she was started on phenoxybenzamine 10 mg BID and encouraged on liberal salt intake. During the course, her blood pressure and heart rate were monitored daily. She underwent right adrenalectomy. Surgical pathology revealed 4.1 cm pheochromocytoma, negative margins with extension to the adipose tissues and vascular invasion, PASS score = 4. Post operatively, patient declined to get labs done. Due to high risk behavior of the tumor, patient needs to be monitored annually for lifelong.

Conclusion: Pheochromocytoma is an uncommon tumor with varied clinical presentation. It can manifest itself widely from being silent to aggressive disease. This warrants high suspicion, early detection and management, thereby reducing the morbidity and mortality. Lately, there has been increased incidence of adrenal incidentalomas owing to widespread use of radiological investigations. We report a case of incidental pheochromocytoma which is biochemically active but clinically asymptomatic. This emphasizes the importance of being more vigilant during the evaluation of adrenal incidentalomas.
Inflammatory Myofibroblastic Adrenal Tumor: An Extreme Rare Cause of Adrenal Incidentaloma
Authors: Elshimy Ghada , Gandhi Anand , Jyothinagaram Sathya G
Published: May 2021

Introduction: An inflammatory myofibroblastic tumor (IMT) is considered a complex disease with a suggested neoplastic nature. It has a variable histological and clinical presentation. Up to now, the exact etiology is still unknown. Various sites such as the lungs (first site described in 1939), the heart, the gastrointestinal tract, and the genitourinary tract have been reported in the literature. The adrenal glands are considered an extremely rare location with no recurrence reported after surgical management. Up to our knowledge, only 9 cases have been described in the literature. The age of presentation was variable (from newborn to 57 years old). Case Report: A 70 years old female with a past medical history of well-controlled diabetes type 2, and hypertension presented with a progressively increasing chronic right flank pain for the past couple of months, associated with 10 lb weight loss. Workup was done and an incidental right adrenal mass was found on CT scan. The mass was 3.2cm x 3.3 cm partially necrotic with adjacent stranding abutting the right adrenal gland and the liver. The opposite gland was normal and there was no evidence of any other mass lesion in the abdomen. MRI adrenal showed 3.2x2.5x3.6 cm solid heterogeneous mass in the right adrenal gland (Hypointense on T1 and T2 weighted images. She had no sign or symptoms suggestive of Cushing and/or pheochromocytoma. Her hypertension was well controlled on lisinopril 10 mg. Hormonal workup was within normal range except for a mild elevation of DHEAS. Given the size of the mass, the worrisome radiological characteristics, and a family history of pheochromocytoma in her daughter, surgical options were discussed with the patient. Subsequently, the patient underwent the right robotic adrenalectomy. The postoperative course was uneventful. Pathology revealed a 6.5x6x 5 cm IMT of the adrenal. The CT scan done 6 months postoperatively didn’t show any recurrence. Discussion: and conclusion: Adrenal IMTs are extremely rare but they should be considered in the differential diagnosis of adrenal masses. Follow-up is warranted since its behavior still remains uncertain. More cases are needed to unmask the true biological behavior and pathogenesis of adrenal IMTs.
Interpreting Normetanephrines-the Significance of Clinical Context
Authors: Kumar Nitya , D’Alessio David A
Published: May 2021

Introduction: Pheochromocytoma ranges in presentation, but the diagnostic hallmarks are increased catecholamine secretion in patients with an adrenal mass. However, interpretation requires consideration of the clinical state.

Case: A 60-year-old man presented with 6 months of episodic flushing, night sweats, fatigue, back pain, and 20-pound weight loss. Vitals were notable for hypotension and mild tachycardia. He was thin with evidence of hyperpigmentation. Contrasted CT showed 15 cm heterogeneous masses of both adrenals and a rib lesion. Plasma normetanephrines were elevated on two separate measures (526 and 1,398 pg/mL, nl <=148). Plasma metanephrines were normal. Urine normetanephrines were increased 4-fold (2,165mcg/g Cr, n 108–524). Labs noted low DHEA-S (2 mcg/dL, n 38–313), high ACTH (204 pg/mL, n 6–50), random cortisol (5.2 mcg/dL, n 3.5–18.3), undetectable aldosterone, and high plasma renin activity (83 ng/mL/h, n 2.9–10.8). Cortisol peaked at 6.7 mcg/dL 1 hour after 250mcg of cosyntropin. MRI revealed over 15cm infiltrating masses arising from adrenals with modest flare on T2 imaging. Dotatate PET/CT showed mild uptake of bilateral adrenals and metastases to liver and bone. He was started on steroid replacement and doxazosin for presumed pheochromocytoma.

He was transferred to our facility where he remained hypotensive despite adequate glucocorticoid and mineralocorticoid replacement. Once stabilized, repeat plasma normetanephrines were insignificant (218 pg/mL, n 0–145) and chromogranin was normal (68 ng/mL, n<93). Biopsy of the rib lesion confirmed diffuse large B-cell lymphoma.

Discussion: Pheochromocytoma classically presents in the outpatient setting with palpitations, diaphoresis, pallor, and paroxysmal hypertension. Rarely, it results in hypertensive emergencies requiring hospitalization. In patients with catecholamine excess and an adrenal mass, pheochromocytoma is usually suspected. 3-fold or more increases of normetanephrines or metanephrines above upper cutoffs are rarely false-positives. However, this assumes clinical stability. Sympathoadrenal activation is a physiologic response to acute illness. Metanephrines in critically ill patients without pheochromocytoma approached those of pheochromocytoma in one study. Levels normalized upon recovery from illness, highlighting the importance of verifying biochemistries once the patient is stable. The degree of elevation in normetanephrines seen in this patient was a physiologic response to adrenal insufficiency and clinical instability. Pathology confirmed lymphoma rather than pheochromocytoma for which he was started on chemotherapy.

Conclusion: Elevated normetanephrines is an appropriate physiological response in the acutely ill. Careful consideration of the clinical picture in conjunction with biochemical data is critical.
Mixed Corticomedullary Tumors of the Adrenal Gland Harboring Both Medullary and Cortical Properties
Authors: Inoue Aiko , Inoue Sachika , Sawai Rui , Hamamatsu Keita , Okazaki Kyoko , Nishizawa Hitoshi , Yamazaki Yuto , Sasano Hironobu , Murabe Hiroyuki , Yokota Toshihiko
Published: May 2021

Adrenal cortex and medulla are derived from mesoderm and ectoderm, respectively. Mixed corticomedullary tumors (MCMTs), comprising an intimately admixed population of both adrenal cortical cells and pheochromocytes in a single adrenal tumor, are extremely rare and its pathogenesis has remained unknown. Here, we report a case of MCMT whose cells co-expressed cortical and medullary antigens in the same tumor cells.[Case description]A 40-year-old woman was referred to our hospital for investigating Takotsubo cardiomyopathy following resection of uterine fibroids. An abdominal CT scan depicted a 24 mm tumor on her left adrenal gland. Her basal serum ACTH, cortisol levels and urinary cortisol were 13.8 pg/mL, 9.5 μg/dL, and 26.5 μg/day respectively. The cortisol level was normally suppressed by an administration of 1 mg dexamethasone (1.4 μg/dL). Plasma renin activity, aldosterone levels and urinary aldosterone were 15.0 ng/mL/h, 122 pg/mL, and 5.0 μg/day, respectively (with administration history of azosemide). On the other hand, her plasma adrenaline and noradrenaline levels were elevated as high as 177 pg/mL and 536 pg/mL, and urinary metanephrine and normetanephrine were 2.12 mg/day and 1.10 mg/day. A 123I-metaiodobenzylguanidine scan revealed high uptake in the tumor. After adequate adrenergic α-receptor blockage, left adrenalectomy was performed. Her postoperative endocrine and clinical findings were normalized without any further complications.[Pathology] Immunohistochemistry (IHC) revealed the presence of MCMT. Cells morphologically consistent with pheochromocytoma and adrenocortical cells were confirmed by immunostaining of chromogranin A and SF-1, respectively. Chromogranin A-positive medullary-derived and SF-1-positive cortical-derived tumor cells were intermixed in the chimeric fashion. In addition, some tumor cells were positive for both proteins, indicating hybrid nature of the cells. Tumor cells of cortical origin expressed CYP11β1, 3β-HSD, p450c21, and p450c17, but not CYP11β2. Non neoplastic adrenal cortex were atrophic, whereas the glomerulosa was hyperplastic positive for CYP11β2, consistent with diffuse hyperplasia and adrenal medullar unremarkable. [Conclusions:]The adrenal tumor was clinically diagnosed as pheochromocytoma, but the pathological findings did reveal cortisol production in the tumor and aldosterone overproduction in the accompanying cortex. This is the first case of MCMT co-expressing adrenal medullary and cortical antigens in the same tumor cells as hybrid cells.
Persistent Hyperkalemia Post-Adrenalectomy for Aldosterone-Producing Adenoma
Authors: Borhan Marisa Khatijah , Sieng Tan Florence Hui
Published: May 2021

Background:Post-operative hypoaldosteronism due to chronic suppression of the renin-aldosterone axis of the contralateral gland can be complicated with hyperkalemia. We describe a case of persistent hyperkalemia post adrenalectomy for aldosterone-producing adenoma. Clinical Case: A 47-year-old male was first diagnosed with hypertension in 2011. He was investigated for secondary hypertension after hospital admission in 2019 for hypertensive urgency and symptomatic hypokalemia (potassium, K 1.9–2.3 mmol/L, n = 3.5–5.0). Subsequent laboratory investigation revealed elevated serum aldosterone (3565 pmol/L, n < 103) with an aldosterone renin ratio of 115 (n < 35). A confirmatory test with saline loading showed an unsuppressed serum aldosterone level of 1840 pmol/L. Adrenal CT reported a 4.1-cm, heterogeneous left adrenal lesion. A diagnosis of primary aldosteronism was made, and he underwent laparoscopic left adrenalectomy in July 2020. Histopathology examination was consistent with adrenal cortical adenoma. Both potassium supplementation and spironolactone were stopped immediately postoperatively. Two weeks later, he developed symptomatic hyperkalemia (K 6.0 mmol/L), requiring hospital admission, and started on potassium binder. Throughout clinic follow-ups, potassium remained high (K 5.4–6.1 mmol/L), despite low potassium diet and potassium binder. His case was co-managed with the nephrology team and given a trial of frusemide and sodium bicarbonate to normalize his potassium. However, after 4 months, he remained hyperkalemic. Repeated serum aldosterone was not elevated (<103 pmol/L). He was then started on fludrocortisone and finally managed to achieve serum potassium normalisation (K 4.1–4.5 mmol/L). Conclusion: This case highlights the importance of monitoring potassium levels in all patients after adrenalectomy, particularly those with clinical risk factors. Retrospective studies by Park et al and Fischer et al reported that a long duration of hypertension, impaired preoperative renal function, older age, and large adenoma size represent risks for developing hyperkalemia postoperatively, whereas the use of mineralocorticoid receptor antagonists preoperatively does not prevent hyperkalemia. Treatment includes a low potassium diet, a high sodium diet, adequate hydration, potassium binder, frusemide, and fludrocortisone. In some cases, hyperkalemia may be prolonged, necessitating long-term fludrocortisone therapy, up to 11–46 months². References: 1. Park KS, Kim JH, Ku EJ, et al. Clinical risk factors of postoperative hyperkalemia after adrenalectomy in patients with aldosterone-producing adenoma. Eur J Endocrinol. 2015 Jun;172(6):725–31. 2. Fischer E, Hanslik G, Pallauf A, et al. Prolonged zona glomerulosa insufficiency causing hyperkalemia in primary aldosteronism after adrenalectomy. J Clin Endocrinol Metab. 2012 Nov;97(11):3965–73.
Pheochromocytoma Presenting in a Elderly Female With a History of Uterine Leiomyoma and Renal Cell Carcinoma
Authors: Rico Jeffrey Gara , Innerfied Ronald
Published: May 2021

Background: Adrenal incidentaloma are masses that are found coincidentally on radiologic imaging usually performed for indications other than evaluation for adrenal disease. Pheochromocytomas are rare, usually sporadic catecholamine-producing adrenal tumors and represent 5% of adrenal incidentalomas. While pheochromocytomas can present on their own, they can also present as part of a spectrum of disease found in certain familial syndromes. We present a case of pheochromocytoma found in a patient with a history of renal cell carcinoma and fallopian tube leiomyoma.

Case Presentation: A 67 year old female with a past medical history of diabetes mellitus type II, end stage renal disease on hemodialysis, hypertension, skin cancer, right fallopian tube leiomyoma, and right renal mass suspected for renal cell carcinoma presented to the clinic for evaluation of a left adrenal mass. Left adrenal mass was incidentally found 3 years ago on CT abdomen for evaluation for renal transplant and noted to be 2.2 cm in diameter. There were also incidental findings of a 1.3cm right renal mass and a 5.6x4.8cm right adnexal mass. Patient underwent robot assisted total laparoscopic hysterectomy with bilateral salpingo-oophrectomy and surgical pathology results showed leiomyoma of the myometrium. Surveillance CT imaging done 3 years after showed the left adrenal mass and right renal mass increased in size with the adrenal mass increasing to 4.3 cm in diameter with central necrosis and right renal mass increasing to 3.2 x 1.3 cm. Screening biochemical test were done, and initial test and confirmatory test confirmed pheochromocytoma. Dexamethasone suppression test and aldosterone/renin ratio results were normal. Surgical pathology confirmed pheochromocytoma and biopsy of the right renal mass 8 months later confirmed renal cell carcinoma.

Conclusion: Majority of pheochromocytomas are sporadic but up to 40% have been identified as inherited in origin due germline mutations. They have been known to present as a part of a spectrum of disease pathologies specific for certain familial syndromes such as Neurofibromatosis Type 1, Von Hippel Lindau Syndrome, Multiple Endocrine Neoplasia Type 2, and Familial Paragangliomas. One relatively uncommon syndrome, Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome due to a mutation in the fumarate hydratase gene, has been known to present with pheochromocytoma in rare cases. Our patient presented with pheochromocytoma, renal cell carcinoma, and uterine leiomyoma which is suspicious for Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome. The diagnosis was not confirmed as genetic testing was not done. Due to a high rate of inherited patterns of pheochromocytoma, routine genetic testing should be done as identification of gene mutations may lead to diagnosis, treatment, and surveillance for patients and their relatives.
Pheochromocytoma Rupture Associated With Systemic Anticoagulation: A Case Report
Authors: Wan WingYee , Graybill Sky Denniston
Published: May 2021

Background: Pheochromocytoma rupture is a rare endocrine emergency. There have been approximately 85 documented cases, and the mortality rate for patients who require emergent surgery is as high as 34% (1).

Clinical Case: A 30-year-old man with no past medical history presented to the Emergency Department with abdominal pain and vomiting. He was hypertensive, tachycardic, and hypoxic. CT Chest Angiogram revealed bilateral pulmonary emboli and a 6.5 x 5.5 x 6.4 cm left heterogenous adrenal mass. His plasma free metanephrines were elevated to 31,173 pg/mL (n<62 pg/mL) with normetanephrines >50,000 pg/mL (n<145 pg/mL). His pulmonary emboli was treated with continuous intravenous heparin, and he was also treated with intravenous fluids and phentolamine due to concern for pheochromocytoma. Within hours, he became hypotensive, and his hemoglobin downtrended from 16.4 g/L to 7.3 g/L (n 14–18 g/L). Repeat CT showed that the adrenal mass had ruptured, enlarging to 15.4 x 9.7 x 10.0 cm. He was taken for an emergent laparotomy with piecemeal resection of the mass; surgical pathology confirmed a pheochromocytoma. Fortunately, the patient recovered well after surgery. After 6 months, his plasma free metanephrines normalized to 15 pg/mL with normetanephrines of 80 pg/mL. His DOTATATE scan was negative for malignancy and his genetic testing was negative.

Conclusion: The patient’s systemic anticoagulation and critical illness likely increased his risk for pheochromocytoma rupture. Standard preoperative pheochromocytoma management, to include aggressive fluid resuscitation and alpha blockade, is important in reducing risk of morbidity and mortality. Biochemical follow up is required, as there is a 16% risk of recurrence.

Reference: (1) Kobayashi T, Iwai A, Takahashi R, Ide Y, Nishizawa K, Mitsumori K. Spontaneous rupture of adrenal pheochromocytoma: Review and analysis of prognostic factors. Journal of Surgical Oncology. 2005;90(1).
Pitfalls of Prenatal Diagnosis guiding Postnatal Management in Congenital Adrenal Hyperplasia(CAH)
Authors: Murthy Deepa Badrinath , Litao Melissa Kaori , Shah Bina Cherryl , Kohn Brenda , Breidbart Emily Nicole
Published: May 2021

Background: 21-hydroxylase deficiency is the most common form of CAH and is associated with a variety of clinical phenotypes (salt wasting SW, simple virilizing SV and non-classic NCCAH). Commonly, there is a strong genotype-phenotype correlation for SW and NCCAH, but this is less predictable with the SV forms. We present a case with prenatal diagnosis of classic CAH which demonstrated genotype-phenotype discordance. Clinical Case: Ex 39 weeker female born to non-consanguineous parents was prenatally diagnosed with CAH based on routine genetic screen. Mother was noted to be a carrier for Intron 2G and father was a carrier of p.I172N both known to be pathogenic variants on CYP21A2. At 23 weeks gestational age, DNA analysis revealed fetus was compound heterozygous for both mutations which is most commonly associated with either SV or SW phenotype. At birth, infant had mild edema of the labia majora which resolved; the clitoris was not enlarged. There was no genital virilization or urogenital sinus. Newborn screen sent at 15 hours of life:17 OHP 132 ng/ml, repeat on DOL 3:77 ng/ml and DOL 13:59.9 ng/ml. High dose cosyntropin stim test on DOL 3 at 0 min: Cortisol not done, 17 OHP 1279 ng/dl; 60 min: Cortisol 12.3mcg/dl, 17OHP 3394 ng/dl. DOL 5 at 0 min: Cortisol 2.7 mcg/dl, ACTH 164.5 pg/ml, 17OHP 803.7 ng/dl; 60 minute: Cortisol 7.6mcg/dl, 17OHP 5920 ng/dl. Using available 17OHP normograms, the infant’s stimulated 17 OHP levels were not consistent with classic CAH. Unstimulated testosterone on DOL 3: 25ng/dl, DOL 5: 14 ng/dl. Ultrasound showed adrenal gland thickness 4mm bilaterally (upper limit of normal). Hydrocortisone (HC) was started on DOL 5 at 35 mg/m2/day after the stim test. On DOL 7, HC was increased to 100 mg/m2/day; fludrocortisone 0.1 mg twice daily and NaCl 0.5 g/day were started (Na 131, K 6.5, plasma renin activity 80.2). Upon discharge (DOL 13), infant was on HC 35 mg/m2/day, Fludrocortisone 0.1mg twice daily and NaCl 2g/day. Doses were adjusted accordingly during outpatient follow up. Currently infant is 4 months of age, thriving and remains on HC 11.3 mg /m2/day, Fludrocortisone 0.05 mg twice daily and NaCl 750 mg daily. Postnatal genetic analysis confirmed prenatal genotype. Conclusion: In general, genotype-phenotype correlation has 80–90% concordance. However clinicians should be aware of genotype/phenotype discrepancies that exist in order to carefully guide postnatal management based on prenatal genetic analysis. Our patient’s 17-ohp was done by LC/MS, which is standard now for most specialized endocrine laboratories. However, the 17-ohp nomograms for CAH, which are frequently used for subtype categorization, are based on RIA levels. Further studies would be helpful in creating an updated normogram using LCMS specifically for the neonatal period, as confirmatory screening of CAH will become more common with the rise in parental prenatal carrier screening.
Pituitary Macroadenoma Masked by Iatrogenic Adrenal Insufficiency: A Diagnostic Blind Spot
Authors: Yee Ng Ivy Hoi , Cheung Elaine Yun Ning
Published: May 2021

Background: Exogenous steroid use is the most common cause of central adrenal insufficiency. Depending on the duration and strength used, it may take months to years for the hypothalamic-pituitary-adrenal (HPA) axis to recover after the steroid is stopped. We report a case of iatrogenic hypoadrenalism with persistent suppression of the HPA axis for 13 years, discovered later to be due to a second pathology.

Case: A 48 year old lady presented in 2005 with weight gain of 20 kg over 1 year and florid Cushingoid features. 9AM cortisol was undetectable (<12 nmol/L). History taking revealed use of oral dexamethasone at various dosages over the past 9 years for her knee pains. A diagnosis of iatrogenic adrenal insufficiency was made. She was started on hydrocortisone replacement, and was advised to stop the over-the-counter steroids. By 2011 her short Synacthen test (SST) showed much improved functioning of the HPA axis (cortisol 182 (0 min) -> 329 (30 min) -> 408 nmol/L (60 min) [N peak>500 nmol/L]), and she was back to her usual body weight. However, subsequent monitoring revealed declining trend of 9AM cortisol from 135 nmol/L (2013) -> 99 nmol/L (2014) -> 57 nmol/L (2015) -> 64 nmol/L (2016) -> 18 nmol/L (2017) [N 166–507 nmol/L]. Hydrocortisone compliance and abstinence from exogenous steroids was confirmed with the patient. The ongoing hypofunction of the HPA axis was continually attributed by multiple physicians to her history of prolonged use of dexamethasone. In 2018, at the age of 60, the lady presented with new onset headaches, blurred vision, and bitemporal hemianopia for 3 months. MRI showed a 1.8x1.8x3.5 cm (WxAPxH) pituitary mass with suprasellar extension compressing the optic chiasm. Blood tests revealed panhypopituitarism: SST cortisol 17 -> 59 -> 49 nmol/L, ACTH 2.7 pmol/L [N <10.1 pmol/L]; fT4 9.5 pmol/L [N 12–22 pmol/L], TSH 0.97 mIU/L [N 0.27–4.2 mIU/L]; LH <0.1 IU/L, FSH 0.52 IU/L (menopause at age of 48); IGF-1 27 µg/L [N 41–279 µg/L]; prolactin 17 mIU/L [N 102–496 mIU/L]. After partial excision of the mass her vision improved, but remained dependent on hydrocortisone and thyroxine supplements. The lesion was pathologically proven to be a pituitary macroadenoma.

Discussion: This case presents the uncommon course of a patient who had almost recovered from iatrogenic hypoadrenalism, only to lapse back into worsened central adrenal insufficiency, as part of panhypopituitarism related to an undiagnosed pituitary mass. In retrospect, the unusually protracted state of hypocortisolemia and the atypical waxing and waning HPA axis should have alerted one to consider alternative etiologies at work. As LH-FSH and GH deficiencies commonly develop before ACTH and TSH deficiencies in most pituitary macroadenomas, a lower threshold for testing the other anterior pituitary hormones followed by imaging of the pituitary could have picked up the tumor earlier in this patient.
Two Cases of Pembrolizumab-Induced Secondary Adrenal Insufficiency
Authors: Kanzaki Akinori , Otsuki Taiichirou , Arii Tohru , Koyama Hidenori , Katayama Satoru
Published: May 2021

Title: Two cases of pembrolizumab-induced secondary adrenal insufficiency Background: Although few cases regarding pembrolizumab-induced secondary adrenal insufficiency were reported, it has recently been published that significantly higher prevalence of human leucocyte antigen (HLA)-DR15, B52, and Cw12 was revealed in 11 Japanese patients with immune checkpoint inhibitor-induced secondary adrenal insufficiency as compared with healthy controls and DR15 might be a predictive marker. This is based on the evidence that DR15 has associations with IL-17-mediated autoimmune disease such as Hashimoto’s thyroiditis, and that anti-programmed death 1 (PD-1) inhibitors activate the Th1 and Th17 pathways. We here introduce two Japanese patients with pembrolizumab-induced secondary adrenal insufficiency from a viewpoint of their HLA typing test results.

Clinical Case: Case 1. A 52-year old male diagnosed with stage IV lung cancer (squamous non-small cell lung cancer) was treated with chemotherapy consisting of carboplatin, nab-paclitaxel, and pembrolizumab. Six days after the fourth cycle of pembrolizumab, he suffered from hypoglycemia and hyponatremia. Endocrinological examination findings showed ACTH and cortisol deficiency throughout the day, after which a diagnosis of secondary adrenal insufficiency was made based on no response shown in insulin tolerance, anterior pituitary function, and rapid ACTH stimulation tests. Pituitary cell antibody-1 was negative, and no evidence of a swollen/atrophied pituitary gland or space occupying lesion was observed in magnetic resonance imaging (MRI) results. Furthermore, Hashimoto’s thyroiditis was suspected based on anti-thyroid peroxidase antibody positivity. HLA typing test results highly corresponded with the reported results (A24, B52, Cw12, DR4, DR15).

Case 2. A 70-year old male was treated with pembrolizumab for recurrence of lung squamous cell carcinoma (stage IV). Two weeks after completion of five cycles, severe diarrhea occurred, suspected to be a side effect of pembrolizumab, which was relieved with temporary use of prednisolone. However, diarrhea recured accompanied with a high fever,

eosinophilia, and acute hyponatremia. Based on results showing deficiency of ACTH and cortisol, adrenal insufficiency was suspected. Anterior pituitary function and rapid ACTH stimulation test results supported that diagnosis, while pituitary cell antibody-1 was negative and MRI findings were not remarkable. Notably, completely different HLA typing test results were observed. Conclusion: Similar to the previous report, HLA-A24, B52, Cw12, DR4, and DR15 were found in case 1, whereas all subtypes including HLA-DR15 were lacking in case 2. We think that it should not be given low priority for cases lacking DR15 and the possibility of an association with IL-17 in such cases is required in feature study.
Unlikely Coexistence of Sporadic Pheochromocytoma and Bilateral Macronodular Adrenal Hyperplasia: A Challenge to Manage
Authors: Dinh Kathryn , Failor Richard A
Published: May 2021

Background: The incidence of bilateral macronodular adrenal hyperplasia (BMAH) is unknown, but growing in an era of increased utilization of imaging. Coexistence of BMAH and pheochromocytoma has not previously been reported.

Clinical Case: A 63-year man presented with enlarging left chest-wall mass found to have a poorly differentiated sarcoma. Staging PET/CT identified a hypermetabolic 2.0 cm left adrenal nodule with SVU of 16.6 concerning for metastasis. Hormonal evaluation included dexamethasone suppression test with 7AM serum cortisol of 24.7 ug/dL (<1.8 ug/dL) without dexamethasone level, serum ACTH <5.0 pg/mL (7.2–63 pg/mL), plasma metanephrine of <0.20 nmol/L (0–0.49 nmol/L), and plasma normetanephrine of 0.76 nmol/L (0.00–0.89 nmol/L). Biopsy of this left adrenal nodule was consistent with pheochromocytoma. By history, he lacked any classical symptoms of pheochromocytoma. Repeat testing demonstrated only slight elevations in normetanephrine (1.3 nmol/L and 1.2 nmol/L); he remains asymptomatic at follow-up 4 months later. However, history and exam revealed central obesity, thin skin, type 2 diabetes mellitus on insulin, and hypertension controlled on three agents concerning for Cushing’s. Repeat evaluation showed AM cortisol of 17.9 ug/dL (<1.8 mcg/dL) with dexamethasone level of 917 ng/dL (180–550 ng/dL), ACTH of 6.4 pg/mL with concordant cortisol of 23.1 ug/dL, and 24 hour urine collection with 0.98 L volume, creatinine of 0.58 g/24h (1–2 g/24hr), and urinary free cortisol of 67 ug/24h (3.5–45) altogether suggesting ACTH-independent hypercortisolism. On review of CT abdomen, he has bilateral adrenal nodules measuring >1cm with bilateral gland enlargement consistent with BMAH. Resection of his left adrenal gland was not pursued due to cormorbidities as well as biochemically-silent nature of his pheochromocytoma. To manage his hypercortisolism, he was recently initiated on osilodrostat after completing radiation therapy for his chest-wall sarcoma.

Conclusion: This is the first case demonstrating clinical, biochemical, and imaging results consistent with bilateral macronodular adrenal hyperplasia and hypercortisolism also found to have a clinically and biochemically silent, biopsy proven pheochromocytoma. This is also a unique use of osilodrostat to manage BMAH.