ResearchPad - adrenal-case-reports-ii https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[SUN-188 Intra-Articular Triamcinolone Injections - a “Slipped” Cause of Cushing’s Syndrome]]> https://www.researchpad.co/article/elastic_article_8763 Background:

Triamcinolone injections are used to treat various orthopedic and rheumatologic conditions; their effects on the hypothalamic pituitary adrenal axis have not been well characterized.

Clinical Case:

A 14 yo female was referred to our clinic for evaluation of low TSH (0.16 µIU/mL) and possible hyperthyroidism. There was no goiter and she appeared euthyroid and had normal free T4 (1.01 ng/dl) but she had typical features of Cushing syndrome (CS), including round facies, thinning of hair, fatigue, truncal adiposity, violaceous striae, facial hirsutism and oligomenorrhea. She was previously healthy and participated in many sports. She did not report any history of exogenous glucocorticoid use but the fasting ACTH (4 pg/ml) and cortisol (0.1 µg/dl) levels were suppressed. Subsequent chart review revealed that she received intra-articular Triamcinolone (TA) to treat “slipping rib” syndrome. This included 3 injections of Kenalog 40 mg/mL, the last in July 2019. Her cumulative TA dose was 440 mg, the equivalent of prednisone 550 mg. Triamcinolone acetonide 1.4 mcg/dL (normal 0-0.1, analyzed by LC-MS/MS) was detected in the urine over 3 months after her last injection.

Conclusion:

- Levels of ACTH and cortisol can be suppressed for several months after intra-articular corticosteroid injections, placing the patient at subsequent risk for adrenal crisis

- In some cases, high doses of Triamcinolone administered by intra-articular injection can cause clinical Cushing syndrome

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<![CDATA[SUN-163 Metastatic Spindle Cell Sarcoma Unmasked by Bilateral Adrenal Hemorrhage Resulting in Adrenal Insufficiency]]> https://www.researchpad.co/article/elastic_article_8759 Introduction:

Adrenal hemorrhage (AH) is rare and can be life-threatening when bilateral AH causes adrenal insufficiency (AI). Risk factors include trauma, stress, sepsis, anticoagulant and antiplatelet use, hematologic disorders, and underlying adrenal tumors. We describe a patient whose bilateral AH led to a diagnosis of an underlying malignancy and caused AI.

Clinical case:

A 71-year-old man with well-controlled HIV presented with fatigue, weight loss, and acute lower abdominal pain.

Four months prior to presentation, he underwent hip arthroplasty. His post-operative course was complicated by multiple pulmonary emboli and a new left 11.6 x 7.3 x 8.9 cm cystic retroperitoneal lesion with a density of 29 Hounsfield units on CT, thought to be a pancreatic pseudocyst or adrenal or retroperitoneal hemorrhage. Since the size remained stable on repeat CT three days later, he was discharged on rivaroxaban. On the day of presentation, he acutely developed severe abdominal and back pain. CT scan revealed a new 8.0 x 7.8 x 7.8 cm right adrenal collection and increased size of the prior left adrenal lesion to 13.1 x 10.6 x 13.0 cm. MRI confirmed bilateral adrenal masses with intralesional AH, as well as numerous peritoneal and retroperitoneal implants not noted on prior imaging.

He remained stable and was managed non-operatively. Sodium (Na) and potassium (K) ranged 134-138 mmol/L (135-145) and 3.7-4.3 mmol/L (3.5-5.1), respectively. On presentation, morning cortisol and ACTH were 11 ug/dL and 27 ng/L (6-50), respectively, with an undetectable aldosterone and PRA 0.65 ng/mL/hr (0.25-5.8). Subsequent ACTH levels were 71 and 102 ng/L, and cortisol levels were 12 and 14 ug/dL. ACTH-stimulated cortisol was 15 ug/dL and free cortisol was 0.88 ug/dL. Plasma metanephrines were normal. Hydrocortisone was started and anticoagulation was held indefinitely. Biopsy of a retroperitoneal implant revealed metastatic spindle cell sarcoma.

Three weeks later, given a persistently low Na of 134 mmol/L and increased K of 4.7 mmol/L, although blood pressure and heart rate were normal, he was empirically started on fludrocortisone. He followed up with oncology and was started on palliative chemotherapy.

Clinical lessons:

AH should prompt evaluation for an underlying etiology. In our patient, we suspect he already had a unilateral adrenal metastasis causing the initial unilateral AH, as he had no other risk factor. Four months later, the subsequent bilateral AH was likely caused by further metastatic spread and exacerbated by anticoagulation therapy.

This case also suggests that AH may preferentially affect the zona fasciculata of the adrenal cortex and cause glucocorticoid deficiency, a phenomenon which has been noted on prior case reports. Our patient only needed hydrocortisone replacement initially, followed by fludrocortisone replacement three weeks later.

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<![CDATA[SUN-155 A Complex Case of Adrenal Insufficiency Associated with NLRP1 Gene Mutation in a Patient with Myopathy and Mitochondrial Cytopathy]]> https://www.researchpad.co/article/elastic_article_8751 Most cases of Addison’s disease are due to an autoimmune response, with the most commonly associated genes belonging to human leukocyte antigen (HLA) complex. Genome wide association studies have shown a significant association of variants of Nuclear Localization Leucine-Rich-Repeat Protein 1 (NLRP1) with Addison’s disease. NLRP1 protein is involved in the assembly of inflammasome which promotes the secretion of interleukin-1β, interleukin-18 and downstream inflammatory responses to regulate inflammation. With underlying myopathy and mitochondrial disease, coexisting adrenal insufficiency may be challenging to identify. A 36-year-old female presented for evaluation of fatigue, myalgia, and dyspnea for several years. She carried a diagnosis of asthma, myopathy, gastroparesis requiring a gastric stimulator, and recently diagnosed adrenal insufficiency secondary to long term fluticasone use. Beside low blood pressure of 91/64 millimetres of mercury, physical exam was unremarkable. Lab findings were significant for dehydroepiandrosterone-sulfate (DHEAS) of 7.0 micrograms per deciliter (mcg/dL), Adrenocorticotropic hormone (ACTH) of 7.2 picograms per milliliter and cortisol of 1.4 mcg/dL. Adrenal insufficiency was confirmed with cosyntropin stimulation test. Methacholine challenge test showed worsening asthma. She was managed with empiric stress dose steroids when indicated. Muscle fatigue progressed despite taking ubiquinol, B100 and carnitine. She was further evaluated with muscle biopsy that showed type two fiber atrophy. Muscle coenzyme Q10 was 0.08 mcg/dL, and citrate synthase was 50% of normal, insufficient for electron transport complex I. Whole exome sequencing showed mutations in NLRP1 in addition to Myosin Heavy Chain 2 (MYH2) and Sodium voltage-gated Channel alpha subunit 4 (SCN4a) both of which are associated with myopathy. She was then started on a short-acting glucocorticoid regimen. While her adrenal insufficiency was initially thought to be secondary to inhaled steroids, subsequent mutation analysis suggested that she was prone to autoimmunity. This case illustrates the association of adrenal insufficiency with NLRP1 mutation. Furthermore, the symptoms of adrenal insufficiency and myopathy can overlap making it difficult to delineate. While so far most studies have dealt with mitochondrial myopathies due to deletions or point mutations in the mitochondrial deoxyribonucleic acid (DNA), a new field of investigation is that of syndromes due to mutations in the nuclear DNA.

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<![CDATA[SUN-185 Severe Hyponatremia and Type 4 Renal Tubular Acidosis (Functional Hypoaldosteronism) Secondary to Trimethoprim]]> https://www.researchpad.co/article/elastic_article_8710 Introduction:

Trimethoprim-sulfamethoxazole (TMP-SMX) is a commonly used antibiotic. We present a case of severe hyponatremia and Type 4 renal tubular acidosis (functional hypoaldosteronism) in a patient treated with TMP-SMX.

Clinical Case:

A 62 year old gentleman with hypertension, dyslipidemia and a surgically repaired abdominal aortic aneurysm developed an aortic graft infection. He was admitted to hospital for acute right lower limb ischemia with embolic phenomena, and underwent surgical graft explantation. He required multiple courses of antibiotics post operatively.

He was initially referred to Endocrinology for severe hyponatremia, deemed likely to be from a salt losing nephropathy secondary to polymyxin. Thyroid function and morning cortisol levels were normal. He was managed with intravenous hypertonic saline and oral salt tablets. The hyponatraemia resolved a week after polymyxin was stopped.

Intravenous TMP-SMX was commenced the next day at 240 mg BD. A week later, the hyponatremia recurred, with concomitant hyperkalemia and a normal anion gap metabolic acidosis.

The serum sodium was 126 mmol/L (reference interval (RI) 135-145) and the serum osmolality 275 mmol/kg (RI 275- 305). Urine studies showed a high urinary sodium (154 mmol/L) and osmolality (481 mmol/kg), consistent with renal salt wasting. The serum potassium rose to a peak of 6.1 mmol/L (RI 3.5 - 5.0), with a normal anion gap metabolic acidosis (bicarbonate 17 mmol/L (RI 21 – 31)). A paired urine pH of 8 pointed to an inability to acidify the urine.

Given the clinical course and laboratory investigations, the diagnosis of TMP-associated hyponatremia and Type 4 RTA was made. Oral resonium was started to correct hyperkalemia, with a combination of oral sodium chloride and sodium bicarbonate used to treat the hyponatremia and metabolic acidosis. Fludrocortisone was not used given the concerns of causing hypertension in a patient with a diseased aortic graft.

The dose of TMP-SMX was gradually reduced with improvement of the acid-base and electrolyte abnormalities, lending weight to our diagnosis. After the dose of the TMP-SMX was reduced to 80 mg BD, the hyperkalemia and metabolic acidosis resolved. The oral sodium chloride and sodium bicarbonate were gradually tailed off and stopped after cessation of the TMP-SMX.

Clinical Lesson:

Trimethoprim blocks the epithelial sodium channel (ENaC) of the principal cells in the terminal portion of the nephron, similar to potassium sparing diuretics like amiloride and triampterene. The resulting hyponatremia, hyperkalemia and metabolic acidosis can be life threatening. Therefore, monitoring of electrolytes and acid base status is important, particularly in susceptible patients or in those where a high dose of trimethoprim is required.

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<![CDATA[SUN-198 Metastatic Progression of Adrenocortical Carcinoma: Phenotypic Transformation to ACTH-Independent Cushing’s Syndrome]]> https://www.researchpad.co/article/elastic_article_8657 Background: Adrenocortical carcinoma (ACC) is a rare malignancy. Around 60% of adrenal carcinomas are functioning tumors and may present with distinctive phenotypes (1). Very rarely, as the disease progresses, changes in secretory patterns may be observed.

Clinical Case: A 39-year-old female presented to the hospital with a 1-month history of abdominal pain associated with hirsutism, weight gain, acne, and amenorrhea. Computed tomography of the abdomen showed a 7 cm left adrenal mass with areas of necrosis as well as presumptive metastatic disease involving the liver and lungs. Biopsy of the adrenal mass confirmed the diagnosis of adrenocortical carcinoma. Initial laboratories were compatible with hyperandrogenemia (increased 24-hour urine 17-ketosteroid level of 106.3 mg/24 hr (n 6.0-15.0) and mildly elevated testosterone of 65 ng/dL (n<45)). Aldosterone, renin, and metanephrines levels were normal. The patient underwent adrenalectomy after 1 month and was placed on hydrocortisone replacement. Follow-up biochemical testing showed a decrease in 17-ketosteroids level to 24.7 mg/24hr. DHEAS and testosterone were persistently elevated. Following discontinuation of hydrocortisone, her 24-hour urine cortisol was normal at 18 ug/24hr, (n 6-24) and ACTH was suppressed at 1.8 pg/mL (n 7-63). She was started on mitotane therapy shortly after.

Three months after initiation of treatment, she was admitted for a pulmonary embolism. At that time, she had clear signs of hypercortisolism, such as weight gain, hyperglycemia, easy bruising as well as purple striae. Progressive metastatic disease with enlarged lung and liver masses was observed in imaging. On this occasion, her morning cortisol was elevated at 35 ug/dL and ACTH was suppressed at 1 pg/mL. Th hyperandrogenemia was more evident this time with DHEAS of 778 ug/dl. Steroid supplementation was discontinued, and ketoconazole was started. An elevated 24-hour urinary cortisol (2085 ug/24hr) confirmed the diagnosis of Cushing Syndrome. Given the progression of disease while on mitotane, the patient was started on chemotherapy with etoposide, doxorubicin, and cisplatin.

Conclusion: This case represents an unusual example of the phenotypic transformation of adrenal cancer resulting in new-onset ACTH-independent Cushing’s syndrome while the patient was on treatment. Awareness of such changes in secretory pattern are important to guide therapy and minimize morbidity associated with hypercortisolism.

Reference: (1) Puglisi S, Perotti P, Pia A, Reimondo G, Terzolo M. Adrenocortical Carcinoma with Hypercortisolism. Endocrinol Metab Clin North Am. 2018 Jun;47(2):395-407.

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<![CDATA[SUN-187 A Case of Adrenal Mass with Elevated ACTH and Cortisol in a Woman with No Cushingoid Features]]> https://www.researchpad.co/article/elastic_article_8608 Background

Adrenal incidentalomas can present with subclinical Cushing’s Syndrome (SCS), which is defined as elevated cortisol levels without overt clinical signs or symptoms. Inaccuracies in ACTH levels due to issues with the assay and non-classic presentation of Cushing’s Syndrome (CS) can delay appropriate diagnosis and timely intervention.

Clinical Case

A 50-year-old female with a history of an incidentally discovered 3.4 x 1.8 cm adrenal mass was referred for evaluation of hypercortisolism (midnight salivary cortisol 0.17 μg/dL, normal < 0.09 μg/dL) with lack of suppression of both ACTH (19 pg/mL, normal 6-50 pg/mL) and cortisol (13.1 μg/dL, normal 6.0-18.4 μg/dL) on overnight 1-mg dexamethasone suppression test (DST). Pheochromocytoma work up was negative.

Her medical history was remarkable for premature ovarian failure at age 40 and osteoporosis at age 48 (Lumbar spine T-score -3.6, Femoral neck T-score -3.7, Hip T-score -2.7).

She denied alcohol abuse and depression screening was negative. She reported high levels of stress and insomnia. She denied muscle weakness, acne, or change to body habitus. Fasting blood glucose was intermittently as high as 212 mg/dl but HbA1c was 5.5%. She did not have a history of hypertension or glucocorticoid use. Her BMI was 20 kg/m2 and she did not appear Cushingoid. A pitutiary MRI showed no evidence of pituitary lesions or enlargement.

Discussion and Follow up

A non-suppressed ACTH made an adrenal source of cortisol unlikely. The working diagnosis was pseudo-CS secondary to stress, loss of diurnal rhythm due to insomnia, or overlooked depression.

She was taking supplements, including biotin, and was asked to discontinue these for two weeks. Repeat 1-mg DST revealed an elevated cortisol of 9.8 μg/dL with a once again non-suppressed ACTH of 20 pg/mL. Her dexamethasone level was 109 ng/dL (normal after 1 mg dexamethasone 180-950 ng/dL), which may suggest slightly faster metabolism. All ACTH levels were run on Immulite assays, which has recently been suggested to be unreliable (1). When repeated using the Roche Assay, ACTH was low at 1.6 pg/mL. Given suppressed ACTH in conjunction with hypercortisolemia and osteoporosis, an adrenal source of CS was confirmed. Diagnosis was further solidified by a DHEA-S level of 11.4 μg/dL (normal 35.4 - 256 ug/dL). She underwent adrenalectomy and pathology revealed adrenal cortical adenomas.

Conclusion

The correct diagnosis of adrenal CS in this patient was delayed due to erroneously higher ACTH result by the Immulite assay. Similar cases have been reported in the literature with the use of Immulite assays for measurement of ACTH leading to invasive diagnostic procedures and even unnecessary pituitary surgery (1).

1.

Greene LW, Geer EB, Page-Wilson G, Findling JW, Raff H. Assay-Specific Spurious ACTH Results Lead to Misdiagnosis, Unnecessary Testing, and Surgical Misadventure-A Case Series. J Endocr Soc. 2019;3(4):763-72.

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<![CDATA[SUN-170 Adrenal Insufficiency Due to Adrenal Hemorrhage]]> https://www.researchpad.co/article/elastic_article_7185 Introduction: Antiphospholipid Syndrome (APS) can involve multiple organ systems but endocrine manifestations are rare. In most cases adrenal insufficiency (AI) is the first endocrine manifestation of APS. The prompt diagnosis of adrenal insufficiency is critical. We present a case of AI associated with antiphospholipid syndrome who was managed successfully. Case presentation: A 50-year-old man was admitted with deep venous thrombosis of the distal left femoral vein extending to the popliteal vein and was started on xarelto, but he developed pleuritic chest pain and dyspnea in 48 hours. CT scan confirmed a pulmonary embolism and patient was treated with heparin drip. Two days following heparin drip patient developed acute bilateral flank pain and hypotension; and CT abdomen showed 2 masses replacing the adrenal glands that were concerning for hematomas. Laboratory results: serum potassium 4.9 mmol/L, serum cortisol 3.3 mcg/dL (reference 7.2–19.4), ACTH level 319 pg/mL (reference 7–53), aldosterone <1.0 ng/dL (reference 0.0–3.0), and plasma renin activity 7.17 ng/ml/hr (reference, 0.15–3.95). Serum antiphospholipid antibody testing showed cardiolipin Ab Ig 140 GPL/mL (reference 0–14), cardiolipin Ab IgM 100 MPL/mL (reference 0–12) and cardiolipin Ab IgA >150 APL/mL (reference 0–11). Further testing showed beta-2 glycoprotein 1 Ab IgG 103 GPI units (reference 1–20), IgM 94 GPI units (reference 0–32), and IgA 150 GPI units (reference 0–25). His hypotension dramatically improved upon administration of IV hydrocortisone and the abdominal pain resolved in 3 days. Upon discharge he was placed on hydrocortisone and continued warfarin therapy. At a 6-week follow-up visit, patient was asymptomatic. Additional lab tests revealed normal plasma renin activity and aldosterone levels. Two years later an ACTH stimulation test confirmed persistent AI. Basal plasma ACTH level was 230 pg/mL (ref 5–50). Additionally plasma renin activity and serum aldosterone levels indicated no mineralocorticoid deficiency. An adrenal CT scan revealed significant long-term interval decrease in size of bilateral adrenals with hypo-attenuating focus in the right adrenal gland, favored to represent post hemorrhage changes without convincing evidence of underlying neoplasm especially given decrease in size compared to 4-years prior. Presently, patient is doing well on hydrocortisone and warfarin treatment. Conclusion: In all cases of adrenal hemorrhage and infarction with unknown etiology, screening with lupus anticoagulant and anticardiolipin antibodies is imperative. Recognition of this high mortality condition will allow for appropriate screening and confirmatory tests leading to prompt diagnosis and timely management.

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<![CDATA[SUN-172 A False Positive Result in Newborn Screening for Congenital Adrenal Hyperplasia (CAH) in a Girl with Beckwith Wiedemann Syndrome]]> https://www.researchpad.co/article/elastic_article_7168 Background: Congenital Adrenal Hyperplasia (CAH) comprises a spectrum of autosomal recessive diseases, resulting in enzymatic defects in the cortisol secretion. CAH newborn screening can avoid neonatal mortality in children with the salt-wasting form and prevent incorrect gender assignments in females. The occurrence of false-positive results creates diagnostic difficulties presenting therapeutic implications. Beckwith Wiedemann Syndrome (BWS) is a congenital disease characterized by somatic overgrowth, increased risk of neonatal hypoglycemia, and development of embryonic tumors. BWS is due to (epi)genetic changes involving growth-regulating genes with good genotype-phenotype correlation. The adrenal gland is frequently involved and may present diffuse cytomegaly of the adrenal cortex1. We reported a BWS newborn girl with a false-positive diagnosis of CAH in the screening. Case report: The patient was born at 39 weeks from an uneventful cesarean section, 5.6kg (>p97) and 52cm (>p97), referred to the Endocrinology service due to abnormal neonatal tests (neonatal 17-OHP: 96ng/mL) collected at 6 days old. At 14 days old, she was 6.3 kg (Z:+5.59), and 58cm (Z:+2.47), BMI: 18.7 kg/m2 (Z:+4.45), and with typical female external genitalia, ruling out the diagnosis of classic CAH. She presented some syndromic characteristics as macroglossia, ogival palate, orbital hypertelorism, hepatomegaly, and umbilical hernia. At 1 month and 14 days old, serum 17OHP was 7.4ng/mL, androstenedione: 6.1 ng/mL, total testosterone: 279ng/dL, 11-deoxycortisol: 2.11ng/mL, cortisol: 5.0ug/dL, and ACTH: 54pg/mL. At five months old she evolved with normalization of serum 17OHP, androstenedione and testosterone levels (1.36ng/mL, <0.50ng/mL, and 37ng/dL, respectively), but still with high DHEAS levels: 2913ng/mL. At 11 months old, DHEAS also normalized, confirming that it was transient hyperactivity of the zona reticulata. A molecular test was performed in a blood sample by MLPA, showing a gain of methylation in the imprinting control region 1 (ICR1) of chromosome 11p15, which controls two imprinted genes, H19 and IGF-2, confirming the clinical diagnosis of BWS. The hypermethylation of ICR1 is largely related to the Wilms tumor. The patient was diagnosed with bilateral Wilms tumor at 11 months old and undergone chemotherapy without adequate response requiring left nephrectomy at 1 year and 5 days old. Conclusion: We presented the first description of false-positive diagnosis of CAH in the newborn screening of a girl with Beckwith Wiedemann syndrome, probably due to a transient overactivation of the zona reticulata. References: 1.Brioude F, Kalish JM, Mussa A, Foster AC, Bliek J, Ferrero GB, et al. Expert consensus document: clinical and molecular diagnosis, screening and management of Beckwith-Wiedemann syndrome: an international consensus statement. Nat Rev Endocrinol. 2018;14(4):229-49.

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<![CDATA[SUN-164 Adrenal Crisis in Early Pregnancy]]> https://www.researchpad.co/article/elastic_article_7166 Nausea and vomiting are common symptoms in pregnancy, ranging from occasional nausea to fulminant and intractable vomiting. Many underlying metabolic disorders can mimic this, primary adrenal insufficiency (PAI) being one of them. Here, we present a case of adrenal insufficiency early in pregnancy.

A 28 year old lady G1P0 at 8 weeks of gestations, with a past medical history of Grave’s Disease, presented to our hospital on 3 occasions over one week with severe intractable nausea and vomiting. On prior visits, she had received intravenous fluids and discharged home. Laboratory work-up was ordered on the third visit and she was found to have severe hyponatremia with level of 111mMol/L. TSH and FT4 levels were both within the reference range. AM cortisol level was low at 2.3mcg/dL. ACTH and renin were both significantly elevated confirming diagnosis of PAI. Intravenous hydrocortisone was commenced immediately with rapid resolution of her symptoms and correction of her hyponatremia. She was followed at the endocrinology clinic, with appropriate up-titration of glucocorticoid and mineralocorticoid doses throughout her pregnancy.

Diagnosis of PAI is usually established prior to pregnancy. Presentation during pregnancy is not common, but it should be considered as a differential diagnosis when symptoms are out of proportion to the gestational status. Normal pregnancy is accompanied by progressive increase in circulating CRH and ACTH, increasing the levels of free cortisol as early as 7 weeks of gestation, rising up to 20-fold by the end of pregnancy. These physiologic changes could explain early presentation of adrenal crisis given insufficient glucocorticoid production. A delay in diagnosis and treatment increases the risk of maternal and fetal morbidity and mortality significantly.

Management of PAI during pregnancy can be challenging as there are no established guidelines and they have mainly been based on observational studies (1). The appropriate selection and dose of the glucocorticoid is important for the treatment of PAI to minimize adverse effects on mother and baby (2). At the time of active labor and delivery, stress doses of glucocorticoids need to be administered to prevent adrenal crisis (3).

In conclusion, early diagnosis and appropriate management of PAI during pregnancy is necessary to sustain a healthy pregnancy.

Bibliography

1 Husebye ES, Allolio B, Arlt W, et al. Consensus statement on the diagnosis, treatment and follow‐up of patients with primary adrenal insufficiency. J Intern Med 2014; 275: 104– 15.

2 Bandoli G, Palmsten K, Forbess C, et al. A review of systemic corticosteroid use in pregnancy and the risk of select pregnancy and birth outcomes. Rheum Dis Clin North Am. 2017; 43(3): 489–502

3 Chen K, Powrie R. Approach to the use of Glucocorticoids in Pregnancy for Nonobstetric Indications. de Swiet’s Medical Disorders in Obstetric Practice: Fifth Edition. 736-741.

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<![CDATA[SUN-182 Rare Case of Adrenocortical Carcinoma with Tumor Extension into the Inferior Venacava, Right Atrium and Right Ventricle]]> https://www.researchpad.co/article/elastic_article_7116 Introduction: Adrenocortical carcinoma is a rare and highly aggressive malignancy with an incidence rate of 1-2 per million population per year. It is an aggressive tumor with early metastasis to lungs, liver, bone and lymph nodes. Venous tumor thrombosis to inferior venacava (IVC), atrium or ventricle is rare and is considered as a tumor extension instead of metastatic disease, but with a poor prognostic outcome.

Clinical Case: We present a rare case of adrenocortical carcinoma with tumor extension into the IVC, right atrium and right ventricle. A 62-year-old female with history of breast cancer on anastrozole presented to the clinic for a routine screening colonoscopy. Patient was noted to have uncontrolled hypertension before the procedure, so was sent to the ER. Upon further interviewing she complained of increasing abdominal distension, hirsutism, and bilateral lower extremity swelling over the past six months. CT abdomen revealed a large 10 x11 x13 cm heterogeneously enhancing mass arising above the right kidney, with extensive tumor extension into the IVC, right atrium and right ventricle. MRI too characterized a large mass in the right adrenal gland with tumor thrombus extension into the IVC, right atrium, and right ventricle. Hormonal studies demonstrated elevated cortisol, dehydroepiandrosterone-sulfate and testosterone levels. A 1 mg dexamethasone suppression test inadequately suppressed cortisol levels, consistent with Cushing’s syndrome due to endogenous over secretion of cortisol. Free plasma and urine metanephrine levels were normal. Plasma renin and aldosterone concentration were within normal limits. With the cooperation of a multidisciplinary team, patient underwent right adrenalectomy with removal of tumor thrombus from right atrium and right ventricle under cardiopulmonary bypass. Surgical pathology confirmed adrenocortical carcinoma. She was started on mitotane as adjuvant therapy. Patient was also noted to have a lung nodule with biopsy showing oncocytic neoplasm favoring metastasis from adrenal cortex. She did receive chemotherapy for the lung metastasis with decrease in the size of the nodule.

Conclusion: Adrenal cortical carcinoma is a rare disease and the venous tumor thrombus to IVC, atrium and ventricle is even rarer and has a poor prognostic outcome. Complete tumor resection is the only curative approach with adjuvant therapies aiming to decrease the risk of recurrence only. Due to the aggressive nature of the tumor and quick development of metastasis, early diagnosis gives the best chance of resection and hence the greatest chances of survival.

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<![CDATA[SUN-191 The Creatinine, the Crib and the Manometer - Navigating the Labyrinth of Primary Aldosteronism]]> https://www.researchpad.co/article/elastic_article_7083 A 21-year-old Ethiopian female with a five-year history of hypertension presented to medicine clinic with headaches and fatigue for two weeks. She was hypertensive to 163/113 mmHg. She had recently moved to the US and no prior medical records were available. She had been taking an unknown antihypertensive until three weeks prior. She was found to have a creatinine of 3.49 mg/dL. Renal ultrasound revealed bilateral, small echogenic kidneys without any evidence of renal artery stenosis. An intrauterine pregnancy was also incidentally discovered. Her aldosterone level was elevated to 486 ng/dL and her renin activity was 1.3 ng/ml/hr, with a ratio of 373, diagnostic of primary aldosteronism. Due to the markedly high ratio, a saline suppression test was deemed unnecessary for confirmation. Her serum potassium was normal at 3.6 mEq, likely due to poor renal clearance. Given renal failure, a CT non-contrast of the adrenal glands was performed with normal findings. She elected to terminate the high-risk pregnancy.

Based upon her young age at presentation, family history of early onset hypertension, grossly elevated aldosterone: renin ratio and unrevealing workup for a primary tumor or hyperplastic adrenals, a diagnosis of familial hyperaldosteronism was considered. She failed a month-long trial of dexamethasone therapy, therefore glucocorticoid remediable aldosteronism was excluded. She was subsequently started on spironolactone with good response. Adrenal vein sampling was considered to find a surgical target for adrenalectomy but could not be performed given worsening kidney function. After discussion with Nephrology she opted for a pre-emptive renal transplant evaluation, rather than pursuing dialysis. Genetic testing for subclassification has been negative for mutations in KCNJ5 and CACNA1H with ongoing testing for novel mutations.

Primary aldosteronism (PA) usually presents with recalcitrant hypertension, hypokalemia and an elevated aldosterone: renin ratio. It is commonly attributed to adrenal adenomas or hyperplasia with familial hyperaldosteronism (FH) remaining a rare etiology. FH is sub-divided into glucocorticoid remediable, type I, and non- glucocorticoid remediable, types II – IV. The initial diagnosis of such a condition during pregnancy and in the setting of worsening kidney disease presents a diagnostic and management challenge as this precludes adrenal vein sampling and contrast imaging. Our case highlights the importance of early screening for PA and illustrates the need for updated guidelines on aldosteronism workup in the setting of ESRD and pregnancy.

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<![CDATA[SUN-186 Case Report: Mifepristone Taper in an Individual with Equivocal Cushing’s Syndrome Screening Tests]]> https://www.researchpad.co/article/elastic_article_7070 We present a 75-year-old male evaluated by the inpatient endocrine service during an admission for hemorrhagic stroke. Approximately 1 year prior to this admission he was started on mifepristone therapy for presumed Cushing’s Syndrome. Initial Cushing’s work-up was equivocal: 1 mg dexamethasone suppression cortisol level of 1.9 and midnight salivary cortisol 167 ng/dl. Random ACTH measurement was not obtained as part of this initial evaluation. Review of prior imaging studies did not demonstrate obvious culprit pituitary nor adrenal lesions. Mifepristone induced hyperaldosteronism, thyroid dysfunction and adrenal insufficiency were demonstrated presumably secondary to cortisol receptor antagonist induced up-regulation of adrenocorticotropic hormone and cortisol. We describe our experience stopping mifepristone and performing re-evaluation. We propose a tapering protocol in the setting of potentially untreated Cushing’s Syndrome and suggest use as a bridge therapy to surgical intervention rather than destination therapy.

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<![CDATA[SUN-166 Primary Adrenal Insufficiency Caused by Underlying Tuberculosis]]> https://www.researchpad.co/article/elastic_article_7033 Introduction

Primary adrenal insufficiency (AI) is a rare endocrine disorder affecting 1 in 100,000 people. Primary AI is a gradual destruction of the adrenal cortex. Etiology includes autoimmune, tuberculosis, histoplasmosis, blastomycosis, adrenal metastases, primary adrenal tumors, and opportunistic infections of HIV. Since aggressive treatment of TB, the incidence of TB adrenalitis has significantly declined, now accounting for 20% of reported cases where as autoimmune causes of AI account for 70%. Most common symptoms are non-specific, and diagnosis is often delayed, with patient initially presenting with a life-threatening adrenal crisis.

Case

Patient is an incarcerated 65 y/o African American male with PMHx of hypothyroidism who was admitted to the hospital for AMS after being found unresponsive in his prison cell. On admission, patient was febrile, hypotensive and tachycardic. He looked disheveled, confused, and lethargic. Other exam findings were negative.

Lab results revealed WBC 11.7/μL, serum sodium 116 mmol/L, serum potassium 5.2 mmol/L, serum glucose 68 mg/dL, serum osmolality 237mOsm/kg, TSH 26.3mIU/L, and random cortisol 1.6ug/dL. ACTH stimulation test revealed pre-challenge cortisol levels 5.1ug/dL, 30-minute 4.9ug/dL and 60-minute 4.5ug/dL. ACTH 1271 pg/mL (normal range 7.2-63.3pg/mL). A normal response is a stimulated cortisol level > 18ug/dl. Chest x-ray revealed left lower lobe pneumonia.

Clinical signs/symptoms and labs were consistent with primary AI. Adrenal crisis was most likely precipitated by underlying pneumonia. Workup was negative for 21-Hydrolase Antibodies, HIV, CMV, and histoplasmosis. However, QuantiFERON-TB Gold Test was positive. Abdominal CT revealed bilateral enlarged non-enhancing adrenal nodules with coarse calcifications. Biopsy of right adrenal gland revealed necrotizing caseating granulomatous inflammation. Biopsy was negative for isolated aerobic, anerobic, fungal organisms, AFB, and mycobacterium PCR.

Due to current findings and high suspicion of TB adrenalitis, patient is currently being treated as culture-negative tuberculosis along with PO hydrocortisone for underlying AI.

Discussion

Adrenal tuberculosis is a rare cause of primary adrenal insufficiency in developed countries. There should be high suspicion for AI when a patient presents with hypotension, hyponatremia, hyperkalemia and/or hypoglycemia. In this case, although patient did not have a positive AFB culture, he did have a positive QuantiFERON-TB Gold Test along with consistent findings on CT and biopsy. Thus, case was concluded to have high suspicion of primary AI secondary to underlying untreated tuberculosis. Prompt treatment with antituberculosis medication, appropriate steroid therapy, along with monitoring of adrenal function, underlying adrenal insufficiency may be reversible if detected in early stages and decrease mortality.

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<![CDATA[SUN-206 A Rare Case of Untreated Congenital Adrenal Hyperplasia Leading to Gender Dysphoria and a Female to Male Transgender]]> https://www.researchpad.co/article/elastic_article_6970 Background: CAH is a common genetic disorder usually diagnosed in early childhood. However, when it is detected in adulthood, different approach and treatment strategies need to be undergone as their needs are generally different from those of children with CAH.

Case presentation: A 49-year-old male with a past medical history of recurrent urinary tract infections was admitted to the hospital with sepsis and was treated with antibiotics. CT abdomen during admission showed an incidental finding of markedly enlarged bilateral adrenal hyperplasia with an 8x5.5x5.8 cm left adrenal mass, as well as two ovaries and a uterus. Upon further history, the patient said he knew that he was born with abnormal genitalia and had a prolonged stay in the hospital immediately after birth and had surgery of his genitals at the age of six months. He was always told by his family that he is a female, although he never felt it, and he continued to identify himself as a male throughout his life.

He only had one menstrual period at the age of thirteen. He participates in sexual activities as a male but was never able to have a normal sex life. He also gave a history of salt cravings, where he consumes dry salt. He was not taking any home medications.

On examination, the patient had a male voice, a beard, male body hair distribution, no breast. The genital exam revealed labia majora, no labia minora. The rest of his examination was unremarkable.

Work up for CAH revealed normal range plasma metanephrines and DHEA. But ACTH, androstenedione, 17-OH progesterone were all elevated (90.4 pg/ml, 2737 ng/dl, and 24191 ng/dl respectively) and levels were all higher after Cosyntropin stimulation test. He was found to have primary adrenal insufficiency with a maximum cortisol level of 13.3 mcg/dl after the stimulation test.

He was started on oral Hydrocortisone and was closely followed by endocrine after discharge where long-term treatment plans were discussed and our patient decided that he wants to continue his life as a male, and was evaluated by Urology as well as OBGYN for left adrenalectomy and hysterectomy with bilateral Salpingo-Oophorectomy that was successfully performed a month later. Pathology of his left adrenals showed adrenocortical hyperplasia without evidence of malignancy. Patient was educated about lifelong corticosteroid treatment and that he would need to start testosterone replacement therapy to keep his male characteristics.

Conclusion: When children with CAH lose follow up and don’t receive treatment early in life, they can develop gender dysphoria, and their approach as adults become more challenging and it needs a multidisciplinary team to treat, address their needs and detect complications of prolonged adrenal stimulation. Additional research to the natural history and optimal interventions is needed to improve outcomes as these cases are not encountered frequently in clinical practice.

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<![CDATA[SUN-184 Pseudohypoaldosteronism Presenting with Salt Wasting Crisis]]> https://www.researchpad.co/article/elastic_article_6847 Pseudohypoaldosteronism (PHA) is due to end organ resistance to mineralocorticoids. It is usually inherited in an autosomal recessive or autosomal dominant pattern, and rarely can a result of the mutation de novo. Zennaro MC, Hubert EL, Fernandes-Rosa FL. Aldosterone resistance: structural and functional considerations and new perspectives. Mol Cell Endocrinol. 2012;350:206-15.10.1016/j.mce.2011.04.023[Crossref], [PubMed], [Web of Science ®] It can be sub-classified into two forms PHA type 1 A involving the kidneys or PHA-1 B which effects multiple organs. PHA type 2 (Gordon syndrome) presents with hyperkalemia and hypertension. Case: Our patient is a 5 week old male who admitted for significant electrolyte abnormalities. He was followed by PCP for failure to thrive. The child was referred to ED with increased difficulty in feeding, lethargy and episodes of emesis. In the ED, the child was in a compensated shock and had a low normal BP: 76/35, HR: 169/min and fast breathing R/R: 80/minute and afebrile. P.E: showed signs of dehydration. Lab work showed: Na: 110 mEq/L, K: 9.3 mEq/L, low Chloride and Ca: 11.1 mEq/L. Endocrinology recommended IVF supplementation with 2 x NS bolus followed by IVF’s at 1.5 times maintenance (D5 + NS), along with administration of Florinef 0.2 mg suspecting CAH. Renin, 17-OHP, random cortisol level and thyroid hormone levels were ordered. Results showed: TSH of 5.30 mcIU/mL and Free T4 of 2.2 ng/dL. Cortisol: 20.5 mcg/dL. He was subsequently admitted to PICU. Septic work-up was negative. He became hemodynamically stable after hydration and did not require the stress dose of hydrocortisone. Repeat Na: 133 mEq/L, K: 4.7 mEq/L, Cl: 102 mEq/L and Glucose: 90 mg/dL. ACTH stimulation test for CAH evaluation was performed, stimulated 17OHP: 88 ng/dl, cortisol: 27.1 mcg/d and normal DOC. Elevated Aldosterone: 632 ng/dl (5-80) and renin level: 351 (6.5-86). A diagnosis of PHA was made and florinef was stopped and the child was started on NaCl supplementation which normalized the electrolytes. Genetic testing was negative for NR3C2, CUL3, KLHL3, SCNN1A, SCNN1B, SCNN1G, WNK4 and showed that the patient is a heterozygous for a variant of unknown significance, c.6276T>A (p.Ser2092Arg) in the WNK1 gene. However, the patient did not have hypertension and urine electrolytes were also normal did not show signs of PHA 2. Conclusion: PHA can present with severe salt wasting crisis. It can be diagnosed clinically. The relationship of mutation and phenotype can be elusive. Course was uncomplicated and he was discharged from the PICU in 6 days. Sodium doses were titrated based on serum levels with eventual dose of 22.5mEq/kg/day and sodium level was 139 mEq/L.

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<![CDATA[SUN-177 A Silent Bomb: A Case of Severe Primary Adrenal Insufficiency in the Context of Adrenal Metastatic Disease]]> https://www.researchpad.co/article/elastic_article_6825 Background: Adrenals glands are the most commonly involved endocrine organ in cancer metastasis due to its abundant lymphatic communication and blood supply. Up to 4% of non-small-cell lung cancers and 71% of lymphomas have bilateral adrenal metastasis. Early detection with hormone replacement can be life-saving.

Clinical Case:

A 58 year old male was admitted for hyperkalemia (potassium 6.4 mmol/L, range: 3.5-5.1) with prolonged PR interval on EKG, hyponatremia (sodium 131 mmol/L, range: 136-145), hypoglycemia (glucose 48mg/dl), and renal function impairment (creatinine level elevation of 1.38 mg/dl from a baseline of 0.94 mg/dl). He had been diagnosed with Stage IVb non-small-cell lung cancer about 20 months prior, and had a known history of chemotherapy, adrenal metastasis and left adrenal gland radiation (20 G in 5 daily fractions) about 10 months ago. For the past 10 months, the patient had reported no weight loss, nausea, vomiting, or other symptoms or signs of adrenal insufficiency, apart from intermittent fatigue, which he had attributed to his lung cancer diagnosis. On review, a previous PET/CT scan showed intense FDG uptake in the bilaterally enlarged adrenal glands, measuring 3.3 x 2.8 cm on the left, and 3.1 x 1.8 cm on the right. His ACTH level was found to be elevated to 1,023 pg/ml (range: 6-63) with borderline low free cortisol level 0.06 mcg/dl (range 0.04-0.35). Aldosterone level was found to be 3.4 ng/dl (range: 4-31), with a renin level of 36.2 ng/ml/hr (range: 0.5-4). Primary adrenal insufficiency was diagnosed, and the patient was started on hormone replacement therapy, which was titrated as outpatient. Now he is continued on a regimen of hydrocortisone 15 mg and 5 mg, at 8 am and 3 pm respectively, and fludrocortisone 0.1 mg daily. In two months, his ATCH level fell from 1,023 to 89 pg/ml with normalization of kidney functions, sodium level (now 137 mmol/L) and potassium level (now 4.8 mmol/L). He gained 4 kg, and has been feeling more energetic and functional on his follow up visits.

Conclusion: Patients with adrenal metastatic cancer may have atypical symptoms and signs despite having severe primary adrenal insufficiency. High risk patients should be monitored, even in the absence of symptoms, for the development of adrenal insufficiency.

Reference:

1. Yamamoto, T. (2018). LATENT ADRENAL INSUFFICIENCY: CONCEPT, CLUES TO DETECTION, AND DIAGNOSIS. Endocrine Practice, 24(8), pp.746-755.

2. Angelousi A, Alexandraki KI, Kyriakopoulos G, et al. Neoplastic metastases to the endocrine glands. Endocr Relat Cancer. 2019.

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<![CDATA[SUN-176 A Case of Aldosterone-Producing Adenoma with Preoperative Use of a Novel Mineralocorticoid Receptor Antagonist Esaxerenone]]> https://www.researchpad.co/article/elastic_article_6773 Background: Esaxerenone is a novel mineralocorticoid receptor antagonist (MRA) with nonsteroidal structure and high selectivity to MR, which became clinically available in Japan in 2019.

Clinical Case: A 57-year-old woman showed a left adrenal incidentaloma (15mm) on MRI. Serological tests confirmed a diagnosis of primary aldosteronism: baseline plasma aldosterone concentration (PAC) was elevated (47.3 ng/dL, n < 15.9 ng/dL), and plasma renin activity (PRA) below sensitivity. PAC after saline infusion was 43.2 ng/dL. Overnight 1mg dexamethasone suppression test was negative. Her blood pressure had been well-controlled with amlodipine 5mg daily. Despite of large amount of potassium supplementation (96 mmol/day orally and 50 mmol/day intravenously), the level of serum potassium remained low (3.2 mmol/L). Adrenal venous sampling (AVS) was performed successfully, showing laterality index of 45.8 on left. Segmental AVS supported aldosterone hypersecretion from the tumor. After diagnosis, esaxerenone was introduced and the patient became normokalemic without potassium supplementation after a week. No adverse effect occurred in a period of two months before surgery. She underwent laparoscopic left total adrenalectomy. The tumor was positive for CYP11B2, consistent with aldosterone producing adenoma (APA). She became normotensive and normokalemic without any medications.

Conclusion: This case illustrates the preoperative effectiveness of esaxerenone on blood pressure and hypokalemia in patients with APA.

Key words: Esaxerenone; mineralocorticoid receptor antagonist; case report; adrenal venous sampling; primary aldosteronism; aldosterone producing adenoma

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<![CDATA[SUN-178 Clinical and Anatomopathological Characteristics of Two Atypical Aldosterone-Producing Adenomas]]> https://www.researchpad.co/article/elastic_article_6656 Background: Aldosterone producing adenomas (APAs) are the most common cause of unilateral primary aldosteronism (PA). In most cases, APAs present as small (<2 cm in diameter) benign appearing nodules on computed tomography (CT). Up to 70% of APAs may harbor KCNJ5 somatic mutations.

Clinical Cases: Case 1. A 33-yr-old man was referred to investigate resistant hypertension (HT). Biochemical evaluation revealed normal K levels, aldosterone (A) of 14.7 ng/dl, renin of 2.1 mUI/L (normal, 4.4-46.1) and A/R ratio of 24.8. Confirmatory testing confirmed PA diagnosis. Hypercortisolism investigation revealed a non-suppressible cortisol after an overnight 1 mg low-dose dexamethasone suppression (8.3 μg/dL), abnormal midnight salivary cortisol, and normal urinary free cortisol, plasma DHEAS and ACTH levels. Computed tomography (CT) scan showed a well-limited mass in left adrenal, measuring 5.8 cm with pre-contrast density of 30 HU and absolute wash-out of 72%. After left laparoscopic adrenalectomy, hydrocortisone was started and adrenal insufficiency confirmed by basal cortisol <3 μg/dL. He presented biochemical cure of PA and improvement in HT control. Histologic examination revealed an encapsulated tumor with glomerulosa-like cells predominance and a Weiss score 1 (clear cells <25%). CYP11B2 staining was positive in 10% and Ki67 in 5% of tumor cells. Case 2. A 58 yr-old woman was referred to investigate an adrenal mass. She had resistant HT and hypokalemia since 2010. Biochemical evaluation revealed hypokalemia (2.8 mEq/L), A of 16.9 ng/dl, renin <1.6 mUI/L and A/R ratio of 10.6. Confirmatory testing confirmed PA diagnosis. Hypercortisolism investigation was negative. CT scan showed a heterogeneous solid mass in the right adrenal, measuring 5.5 cm with pre-contrast density of 30 HU and absolute wash-out of 77%. After laparoscopic right adrenalectomy, histologic examination revealed an encapsulated tumor with glomerulosa-like cells predominance and a Weiss score 2 (clear cells < 25% and > 1/3 diffuse architecture). CYP11B2 staining was positive in 30% and Ki67 in 5% of the cells. She presented biochemical cure of PA and improvement in HT control. Genetic investigation for somatic KCNJ5, ATP1A1, ATP2B3 and CTNNB1 was negative in both cases.

Conclusion: We describe two rare cases of APAs that presented as large and suspicious tumors, without somatic mutations in genes associated with APAs.

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<![CDATA[SUN-201 Adrenal Insufficiency After Treatment for Vaping Associated Pulmonary Injury]]> https://www.researchpad.co/article/elastic_article_6647 Background: In 2019 a record number of patients were admitted to our children’s hospital with e-cigarette or vaping-associated lung injury (EVALI). The majority of patients were treated with high-dose prednisone therapy including 3 days of 1000 mg daily followed by a 4 week wean. Because of the concern for iatrogenic adrenal insufficiency, all patients were then placed on a 3-4 weak hydrocortisone taper followed by ACTH stimulation testing. The purpose of this study is to document the incidence of iatrogenic adrenal insufficiency following a 2 months glucocorticoid wean. Methods: All patients seen by the Pulmonary team for EVALI who also received high dose prednisone therapy were referred to Pediatric Endocrinology for ACTH testing. A low dose (1 mcg) ACTH stimulation test was performed with cortisol measurements at baseline, 30 minutes, and 60 minutes. A passing result was any cortisol over 18 ug/dl. Results: An anticipated 20-25 patients will have had ACTH stimulation testing by the time of abstract presentation. Of those that have already completed testing, three of four patients failed the first time. Discussion: High-dose prednisone therapy for EVALI is associated with significant rates of iatrogenic adrenal insufficiency, even after slow hydrocortisone wean. Structures need to be implemented to teach patients about adrenal insufficiency prior to hospital discharge and organize adequate post-discharge follow-up until HPA function returns.

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<![CDATA[SUN-194 Adrenal Incidentaloma to Pheochromocytoma (Variant of Unknown Significance of Von Hippel Lindau Syndrome, VHL)]]> https://www.researchpad.co/article/elastic_article_6593 Introduction

The majority of adrenal masses are found incidentally during imaging for non-adrenal causes. Approximately 5% of adrenal incidentalomas have proved to be pheochromocytomas. The majority of incidentalomas are benign and non-secretory.

Case

A 73 years-old white male with pre-diabetes and morbid obesity has been followed by endocrine service for right adrenal incidentaloma overall several years. A 1.6 cm right adrenal nodule with 31 Hounsfield Unit was found incidentally in 2009 CT abdomen for abdominal pain. It was a lipid poor adenoma with >60% absolute contrast washout in 10 minutes. Biochemically it was non-secretory. The size of nodule was gradually increased over next seven years measuring at 1.9 x 1.6 cm in 2010 and 2.1 x 1.6 cm in 2012 but remained non-secretory. In 2015 CT scan, it was measured at 3.0 x 2.3 cm with absolute washout value of 45% and relative washout value of 34%. The size was overall stable again for next three years measuring at 3.2 x 2.2 cm in 2018 scan. Repeat plasma and urine metanephrine were about 2-folds higher than upper normal reference level in 2015 and 3-folds higher in 2017. Clinically he was asymptomatic except anxiety. He has normocalcemia. He underwent laproscopic right adrenectomy after alpha blockage with doxazosin. Pathology showed 4.5 cm pheochromocytoma with positive chromogranin and synaptophysin. Fulgent paraganglioma-pheochromocytoma comprehensive panel with negative for RET,NF1,FH,SDHB,SDHD,SDHC,SDHAF2,SDHA,MAX,TMEM127 and VHL but noted to have heterozygous VUS of VHL c.205>G(p.Arg69Gly). He has no significant family history or personal history to suggest VHL.

Discussion

In a patient with lipid poor adrenal incidentaloma, pheochromocytoma should be ruled out biochemically with either plasma or 24hr urine fractionated metanephrine. Both tests have similar specificity and sensitivity. Even with initial negative biochemical assessment, repeat screening should be performed annually based on clinical suspicion and radiology characteristics. Imaging can be performed annually or biannually to assess the stability of nodule. VHL is an autosomal dominant hereditary disease with del/dup mutation in the VHL gene and associated with multisystem tumor such as CNS or retinal hemagioblastomas, RCC, pheochromocytoma, pancreatic NET, endolymphatic sac tumor, epididymal and broad ligament cystadenoma and visceral cysts.

Learning points

Lipid poor adrenal incidentaloma needs interval biochemical and imaging follow up. The frequency of monitoring can be individualized based on clinical suspicion and radiology findings. Pheochromocytoma can be clinically silent especially if it is small, however, it can be lethal with late or missed diagnosis. This is the first published case report of c.205C>G VHL variant associated with pheochromocytoma.

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