bluuebunny/crossref_metadata_2025_split huggingface dataset:
Androgen Secreting Adenoma Co- Secreting Cortisol First Diagnosed During Pregnancy
Authors: Al Ghareeb Zahra , Alwosaibi Abdulaziz , Alobaidan Hoor 
Published: May 2021

Abstract
Background: Pure androgen secreting adenoma is rare (1) and rarer to have an adenoma that is co-secreting androgen and cortisol, and extremely rare to have it diagnosed during pregnancy. In female, an elevated serum testosterone level with normal adrenal androgens is usually regarded as ovary origin (2). Here we report an unusual case of pregnant woman with markedly elevated serum testosterone level and elevated cortisol that first presented during pregnancy. Clinical Case: A 32-year old lady who is 32 weeks pregnant, presented with signs and symptoms of Cushing and acute hirsutism developed and advanced during pregnancy. Clinically She had hypertension, gestational diabetes with sever hirsutism and virilization. Fasting total testosterone was high (52 nmoL/L n 0.2–2.9 nmoL/L), DHEAS (1.98 umol/L n 0.51–11 umol), 24 hours urine cortisol (1343 nmoL/24 hrs n 11.8–485 nmoL/24 hrs), ACTH (0.220 pmol/L n 1.6–13.9pmol/L). Adrenal MRI without contrast showed a large right adrenal mass of 6.5 x 6.2 x 5.3 cm, of heterogenous signal in all pulse sequences, with limited assessment due to the lack of IV contrast. During admission,the patient’s liver enzymes were gradually increasing which lead to the decision of an elective C-section at 34 weeks gestation followed by right robotic adrenalectomy after ruling out pheochromocytoma. The product was viable and healthy baby boy. The immediate post-op hormonal profile showed normalization of urinary cortisol and serum total testosterone level. Histopathology report confirmed an Adrenocortical adenoma. The patient was discharged on the 3rd day post-op on hydrocortisone replacement therapy. The hydrocortisone doses were gradually tapered down tell stopped. The course of follow up was uneventful, two years following the surgery, she got another pregnancy with no obvious complications.
Conclusion: Co- existing testosterone and cortisol secreting adrenocortical adenoma is a rare tumor, diagnosis and management during pregnancy is challenging, with surgical resection being the only possible definite management.
References: (1) L. Barzon, N. Sonino, F. Fallo, G. Palù, and M. Boscaro, “Prevalence and natural history of adrenal incidentalomas,” European Journal of Endocrinology, vol. 149, no. 4, pp. 273–285, 2003.(2) Zhou, Wb., Chen, N. & Li, Cj. A rare case of pure testosterone-secreting adrenal adenoma in a postmenopausal elderly woman. BMC Endocr Disord19, 14 (2019). https://doi.org/10.1186/s12902-019-0342-y
Cushing Syndrome in Carney Complex: Unilateral or Bilateral Adrenalectomy?
Authors: Vitellius Géraldine , Donadille Bruno , Decoudier Bénédicte , Deguelte Sophie , Bertherat Jérôme , Delemer Brigitte 
Published: May 2021

Abstract
Carney Complex (CNC) is a rare multiple endocrine syndrome dueto PRKR1A germline mutations. Primary pigmented nodular adrenal disease (PPNAD), the most frequent manifestation of the disease is responsible for non-ACTH dependent Cushing syndrome and bilateral adrenalectomy is the recommended treatment. We had followed up a CNC family with mainly Cushing syndrome disease secondary to PPNAD for more than 40 years over 2 generations. Six members carry the disease and present a germline mutation of PRKR1A, 4 women and 2 men. One patient accidently died one year after surgery and the others 5 patients were regularly followed up. The index case, a 25 years woman, was diagnosed with Cushing syndrome in 1972 with hyperandrogenism, short stature and mild manifestations of hypercortisolism. Unilateral adrenalectomy was performed on the side of a nodular adrenal and pathology described PPNAD. Her sister was subsequently diagnosed and treated the same way. The 2 sisters did well, with pregnancies for both of them but different post surgery hormonal results. The index case had partial cortisol deficiency with persistent low cortisol level at 108 nmol/L. Her sister presented a moderate increase in cortisol in the evening or after dexamethasone at 306 nmol/L at last evaluation. The only events possibly associated to hypercortisolism in this patient were central overweight and three episodes of spontaneous pulmonary embolism and veinous thrombosis. Their 2 brothers were evaluated at 17 and 39 years while they developed cushing syndrome signs (round face, HTA, amyotrophy and fatigability). As CNC have been recognized at this time by Dr Carney, bilateral adrenalectomy was performed in one patient who died accidentally a few months later. His brother chose unilateral adrenalectomy on the side of the macronodular gland, recovered hypercortisolism signs and still needs adrenal substitution. The daughter of the index case demonstrated at 21 years old a mild Cushing syndrome and chose unilateral adrenalectomy like her mother. Symptoms resumed without any recurrence during 20 years follow up. The daughter of the patient II.2 was diagnosed earlier at seven years of age because she developed hyperandrogenism, central weight gain and growth arrest due to Cushing syndrome. Bilateral adrenalectomy was successfully performed and adrenal substitution was prescribed. Surprisingly, adrenal function seemed to recover 5 to 6 years post surgery and treatment was decreased then stopped. Adrenal CT scan did not show any residual gland but noriodocholesterol scintigraphy confirmed bilateral adrenal uptake. She is now mother of 2 and present a near normal cortisol circadian rythm without any treatment. Finally, we showed in this long-term study that unilateral adrenalectomy in PPNAD could be an option for the treatment of mild Cushing syndrome in adults. Recovery after bilateral adrenalectomy occurred in one patient.
Endocrinopathies Associated With High Dose Methadone
Authors: Farmer Charles C , Agarwal Monica 
Published: May 2021

Abstract
Introduction: The opioid epidemic is a public health crisis and clinicians should be aware of the many under-recognized endocrinopathies associated with opioids. Herein, we present a case that exemplifies the endocrine-related adverse effects of methadone therapy.
Clinical Case: A 43-year-old Caucasian female with chronic back pain with opioid dependence, high dose methadone use (195 mg daily), and diabetes presented with refractory hypoglycemia. She was diagnosed with ketone prone diabetes eight months prior. She had since been weaned off insulin and her most recent HbA1c was 4.2%. During this time, she had an intentional weight loss of 60 pounds. On examination, she had bilateral lower extremity pitting edema with scaly plaques on the extremities. Laboratory tests showed C-peptide of 0.8 (0.9–7.1 ng/mL), insulin level of &lt; 2 (3–25 mcIntUnits/mL), proinsulin of 4.6 (&lt;18.8 pMol/L) with concurrent glucose of 48 mg/dl. She failed the ACTH stimulation test with 60 minute cortisol of 16.8 mcg/dL and was started on prednisone for adrenal insufficiency (AI). The pituitary and adrenal were normal on imaging. Her albumin was 1.5 (3.7–5.5 gm/dL) and she had vitamin and micronutrient deficiencies including copper, zinc, thiamine, selenium, and vitamin A. The insulin antibody test, paraneoplastic panel, celiac panel, A1 antitrypsin test, EGD, and colonoscopy were all non-revealing. A liver biopsy showed glycogenic hepatopathy. She improved clinically after prednisone initiation and treatment of malnutrition. The hypoglycemia improved but did not resolve as she refused to reduce methadone dose.
Discussion: The proposed mechanism of opioid-induced AI is the inhibitory effect on the hypothalamic-pituitary-adrenal axis, similar to the effect on the gonadal axis which causes hypogonadism. The risk for hypoglycemia is increased in patients taking more than 40 mg of oral methadone per day, and although the mechanism remains unclear, it is independent of adrenal function. Our patient had adrenal insufficiency and hypoglycemia related to methadone, which was further complicated by malnutrition. The glycogenic hepatopathy is a benign reversible condition that is believed to be a consequence of fluctuation in glucose levels.
Conclusion: Given the life-threatening nature of adrenal crisis and the overlap in symptomatology with opiate overdose, clinicians should be prompt in evaluating for endocrinopathies in patients on chronic high dose opiates, and patients should be appropriately counseled on the potential consequences of methadone use.
References: 1.Flory, J. H., et al. (2016). Methadone use and the risk of hypoglycemia for inpatients with cancer pain. JPSM, 51(1), 79–87.2.Li, T. et al. (2020). Prevalence of Opioid-Induced Adrenal Insufficiency in Patients Taking Chronic Opioids. JCEM, 105(10), dgaa499.
Giant Adrenal Pheochromocytoma Presenting With Stroke
Authors: Alsaud Arwa , Karuppasamy Gowri , Al-Owainati Buthaina , Al-Janahi Ibrahim 
Published: May 2021

Abstract
Background: Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumours arising from the adrenal medulla or from paravertebral ganglia of the sympathetic chain(1). The tumours commonly produce one or more catecholamines: epinephrine, norepinephrine, and dopamine leading to a classic triad of presentation with pounding headache, profuse sweating, and palpitations occurs in spells; However, one in 10 patients may be completely asymptomatic and the diagnosis of PPGL is frequently missed(2).
Care Report: A 29 years old African female presented with one-month history of throbbing headache, palpitations, profuse sweating, and unintentional weight loss. Her previous medical history and family history was unremarkable. She was found to have accelerated hypertension and a small lacunar infarct and some suspected subarachnoid hemorrhage on MRI head but was clinically silent. Investigation for secondary causes of hypertension revealed high metanephrine in urine and her imaging showed giant adrenal mass suggestive of pheochromocytoma.
CT Abdomen of large left adrenal necrotic solid mass lesion with heterogenous enhancement of its solid components measuring 6.5 x 6.1 x 7 cm in maximum AP, TR and CC dimensions respectively.
She was scheduled for open resection and left adrenalectomy after approximatly10 day and was treated with high-sodium diet, alpha blockers, and beta blockers perioperatively. Histopathology examination revealed Pheochromocytoma measuring 8 x 7 x 5 cm with diffuse growth &gt;10% of tumor volume with central necrosis; PASS =4, which has malignant potential. She recovered well post operatively and required no further antihypertensive therapy or hormonal replacement, follow up hormonal profile and imaging with Iodine-123 metaiodobenzylguanidine (MIBG) scintigraphy were negative for remnants or metastasis,
further evaluation with gallium DOTATATE PET CT and molecular genetic testing was considered, but it was not available.
Conclusion: Pheochromocytoma is a rare cause of secondary hypertension with a variable clinical presentation. Episodes of tumoral catecholamine release, are thought to be responsible for the high prevalence of cardiovascular emergencies, such as myocardial infarction, heart failure, and stroke as a complication of hypertensive crisis. Timely diagnosis and treatment are crucial to prevent life-threatening complications.
Graves’ Disease Presenting as Adrenal Crisis in a Patient With Congenital Adrenal Hyperplasia
Authors: Ibraheem Hamad Mohammad Khair Ahmad , Karuppasamy Gowri , Abdalrubb Abeer , Baagar Khaled Ahmed 
Published: May 2021

Abstract
Background: Adrenal crisis (AC) is a life-threatening condition that occurs either as the initial presentation of adrenal insufficiency or in patients who are known to have hypoadrenalism, when a precipitating acute stressor outweighs the mineralocorticoid and glucocorticoid supply. It is known that exposure to high levels of thyroid hormones in the presence of hypoadrenalism may precipitate AC.Graves’ disease (GD), as a precipitant of AC in patients with congenital adrenal hyperplasia (CAH), has been rarely described in the literature. Clinical Case: A 15-year-old male with classic CAH diagnosed since birth when he had vomiting and darkly pigmented skin. He was on regular follow-up with his endocrinologist in his home country. For an unclear reason, he was on hydrocortisone 40 mg daily in divided doses. The patient presented to the emergency department with nausea, vomiting, loose stool, dizziness, and fatigue for 5 days. On examination, he was conscious and oriented but looked tired. He had a temperature of 36.8°C, blood pressure (supine) 132/78 mmHg (standing blood pressure could not be taken because the patient was dizzy), pulse rate 130/minute, and respiratory rate 17/minute. Otherwise, the physical exam was unremarkable. Initial laboratory investigations showed sodium 114 (136–145 mmol/L), potassium 6.0 (3.5–5.1 mmol/l), chloride 83 (102–104 mmol/L) and Bicarbonate 14 (22–29 mmol/L). Serum creatinine, complete blood count, C-reactive protein (CRP) and procalcitonin levels were within normal. He was treated for AC with stress doses of hydrocortisone intravenously, and normal saline intravenous infusion. He showed a gradual improvement of his symptoms with normalization of the electrolytes. Thus, he was switched to oral hydrocortisone replacement 15 mg am and 10 mg in the afternoon. Nevertheless, his pulse rate was 105 -110 / min. Therefore, thyroid function test (TFT) was done and revealed TSH 0.3 (0.5–4.3 mIU/L) and FT4 30.6 (12.9–20.6 pmol/L). Thyroid uptake scan showed a mildly enlarged thyroid gland with homogeneous and slightly increased radiotracer uptake suggestive of GD. Thus, propranolol and carbimazole were prescribed in addition to hydrocortisone. Then, the patient was discharged after proper education about precipitating factors of AC. Later on, the patient appeared for his clinic appointment, he was clinically well with normal vital signs, serum electrolytes, and TFT. Propranolol was stopped, carbimazole dose was adjusted, and he was maintained on hydrocortisone.
Conclusion: Unrecognized Graves’ disease was the precipitating factor of the adrenal crisis in this patient with CAH. Despite the rarity of the association, a high index of clinical suspicion for unusual acute stressors is very important for proper management of AC and to prevent future recurrence.
Hypertension and Hirsutism in a Young Female: A Rare Form of Congenital Adrenal Hyperplasia?
Authors: Polavarapu Preethi , Kotwal Anupam 
Published: May 2021

Abstract
Background: Rare forms of congenital adrenal hyperplasia (CAH) especially can be a diagnostic and management challenge. We present a case of hypertension and hirsutism with elevated mineralocorticoid and sex steroid precursors concerning for non-classic rare form of CAH.
Clinical Case: A 22 y/o female was evaluated in our endocrinology clinic for primary hypertension and hirsutism (modified Ferriman-Gallwey score of 12) but without menstrual irregularity, clitoromegaly or deepening of voice. Family history was significant for hypertension and hirsutism in her mother. Renal and pelvic ultrasonographies were normal. CT abdomen showed thickened bilateral adrenal glands. Case detection testing was positive with PAC/PRA of 19.4/0.4 however intravenous saline suppression test suppressed aldosterone to 5 ng/dL, hence ruled out primary aldosteronism. Cortisol suppressed to 0.6 mcg/dL after 1 mg overnight Dexamethasone, hence ruled out Cushing’s syndrome; prolactin and TSH were normal, serum HCG was undetectable. This prompted work up for other endocrine causes of hypertension and hirsutism which revealed follicular phase elevated dehydroepiandrosterone-sulfate of 772 mcg/dL (35–430), pregnenolone of 603 ng/dL (15–132), 17-hydroxypregnenolone of 1516 ng/dL (&lt;226), 11-deoxycortisol of 39.4 ng/dL (&lt;32); but normal 17-hydroxyprogesterone of 36.8 ng/dL (15–70), androstenedione of 1.12 ng/mL (0.26–2.14) and free testosterone of 26 ng/dL (9–44). 250-mcg ACTH administration stimulated cortisol to 24.6 mcg/dL, pregnenolone to 1478 ng/dL, 17-hydroxypregnenolone to 1716, 11-deoxycortisol to 64.2 ng/dL but 17-hydroxyprogesterone only stimulated to 59.9 ng/dL. We initiated spironolactone at 12.5 mg increased to 25 mg daily, which normalized her blood pressure. She was counseled regarding its teratogenicity but is she declined birth control, as she was not engaging in heterosexual intercourse. Urinary steroid analysis and genetic testing were pending.
Conclusions: Hypertension and hirsutism accompanied by elevated pregnenolone, 17-hydroxypregnenolone, 11-deoxycortisol and dehydroepiandrosterone-sulfate, however, normal baseline as well as stimulated 17-hydroxyprogesterone, raise concern for co-occurrence of partial 3-betahydroxysteroid dehydrogenase deficiency in addition to non-classic 11-betahydroxylase deficiency. Management with mineralocorticoid receptor antagonist helped control hypertension.
Large Invasive Adrenal Cortical Carcinoma in a Patient With Neurofibromatosis Type I
Authors: Sandoval Brenda G , Morales Maria Del Mar Felix , Wortham Joy , Koops Maureen , Granda-Rodriguez Ramona , Bruder Jan M 
Published: May 2021

Abstract
Background: Adrenal cortical carcinoma is a rare neoplasm. Adrenal cortical carcinoma has previously been reported in less than 10 cases of patients with Neurofibromatosis Type I. Clinical Case: A 44-year-old Hispanic man with Neurofibromatosis Type I (NF1) presented with progressive hypoxia, tachypnea and abdominal pain. Intubation was required with 100% FiO2. CT angiogram of the chest and abdomen showed a 9.5 cm left adrenal mass with tumor thrombus in the left adrenal vein, distal left renal vein, IVC extending into the right atrium, suggestive of an adrenocortical carcinoma. Café-au-spots, neurofibromas and Lisch nodules were seen on physical exam but no signs suggestive of a functional adrenal cortical carcinoma. Transthoracic echocardiogram demonstrated a large well circumscribed echo-dense mass filling the right atrial cavity. Hemodynamically he was unstable with labile blood pressures due to right atrium thrombus burden. He was supported pending pheochromocytoma investigation. Biochemical work up revealed an elevated 24-hour free cortisol concentration of 95.9 ug/d (&lt;=60ug/d) with a normal 24-hour urine metanephrine and normetanephrine [140ug/d (55-320ug/d) and 448 ug/d (114-865ug/d]. Plasma free metanephrine level was normal 0.43 (0.00-0.49nmol/L) and the normetanephrine levels was increased at 2.7 (0.00-0.89nmol/L) consistent with stress response. Serum aldosterone level and renin activity with potassium and DHEA-S levels were normal. Once pheochromocytoma was ruled out, he successfully underwent a left nephrectomy, left adrenalectomy, IVC thrombectomy, right atrium thrombectomy under a multidisciplinary team of surgeons. Surgery was well tolerated and he was discharged home 11 days later. Pathology confirmed adrenal cortical carcinoma, stage 4, with involvement of endocardium and left renal vein with mitotic count greater than 20/50 high-power fields, consistent with a high-grade tumor. Summary: Patients with NF1 have a higher predilection to develop tumors including pheochromocytoma, paraganglioma, gastrointestinal stromal tumor, and pancreatic neuroendocrine tumor. NF1 association with adrenal tumors is well known, most commonly pheochromocytomas which occur in 0.1–5.7% of patients with NF1. However, based on a literature search there have been less than 10 case reports which postulate an association between NF1 and ACC. Genetic analysis of these reported cases suggest a loss of heterozygosity at the NF1 locus as a possible explanation of development of ACC in patients with NF1. Conclusion: Adrenal cortical carcinoma is rare but should be considered in a patient with NF1 and adrenal mass when plasma/urine metanephrines are not suggestive of pheochromocytoma.
Nivolumab Induced Multiple Endocrinopathies; Adrenal Insufficiency and Primary Hypothyroidism in a Patient With Stage IV Gastric Cancer - A Case Report
Authors: Abdelmasih Randa , Abdelmaseih Ramy , Gandhi Rima , Faya Marines , Vesely Josef James Karl 
Published: May 2021

Abstract
Introduction: Nivolumab is a revolutionary immune check point inhibitor (ICI) that changed the world of oncology. It prevents interaction of Program Death Receptor-1 (PD-1) and Program Death Ligand-1 (PD-L1) releasing a cascade of anti-tumor response. However, it has been associated with wide range of autoimmune side effects including gastrointestinal, hepatic, and endocrine side effects. The incidence of nivolumab induced endocrinopathies is relatively rare but increasingly reported. Adrenal insufficiency occurring in &lt;1% of patients, hyperthyroidism in 15.3% and subclinical hypothyroidism in 4.2%. Case Presentations: 81 year old male with stage IV stomach cancer treated with Nivolumab. Prior to immunotherapy initiation, a set of baseline hormones was obtained and was within normal range. 6 months after, routine monitoring showed elevated thyroid stimulating hormone 6.33 mU/L and low FT4 0.59 ng/dL and FT3 0.1 ng/dL. Patient was started on thyroid replacement therapy. After 1 year of Nivolumab therapy, he presented with dizziness and orthostatic hypotension. Laboratory testing was remarkable for low sodium 130 mEq/L, which raised concerns for adrenal insufficiency. Subsequently, ACTH stimulation test showed low cortisol level 15 mcg/dL. Morning cortisol was also low 1.3 mcg/dL. Other pituitary hormones were normal. Patient was started on hydrocortisone with subsequent improvement of symptoms. Discussion: Nivolumab is a human monoclonal antibody that blocks PD-1 and turns off the tumor mediated immune system inhibition. In the meanwhile, ICI also disrupt normal immune signaling mechanisms that lead to decrease immune tolerance and autoimmune diseases. The mechanism of thyroid dysfunction due to ICI remains unclear. PD-1/PD-L1 blockade could induce thyroiditis by diminishing regulatory T cells function. Disruption of interaction between PD-1-expressing lymphocytes and PD-L-expressing thyrocytes –which protects the thyroid gland from autoimmunity– leads to infiltration of the thyroid with autoreactive T and B lymphocytes. Nivolumab induced Adrenal insufficiency is an extremely rare and unclear event, currently, there is no clear evidence that pituitary cells express PD-1. Recently, it was found that the PD-L1 and PD-L2 are expressed in mouse anterior and intermediate pituitary gland, but not the posterior pituitary. This suggests the possibility that specific injury can take place affecting only certain anterior pituitary cells, such as those producing ACTH. Awareness of such endocrinopathies is crucial. Patients should have certain baseline of laboratory data prior to therapy initiation and over the course of treatment. The risk of endocrinopathies is greater at the start of treatment, justifying closer monitoring every visit over the first 6 months, followed by regular monitoring every second visit over the next 6 months and less frequently thereafter.