Bilateral Nodules Research Articles

Diagnosis of Sertoli-Leydig Cell Tumor of the Ovary Complicated by the Pattern of Hyperandrogenemia and Results of Imaging

Introduction: Virilization in a postmenopausal woman requires evaluation for an androgen-secreting tumor. The differential diagnosis includes adrenal carcinomas and adenomas and Sertoli-Leydig cell tumors, granulosa-theca cell tumors, and hilus-cell tumors of the ovaries. We present a case of virilization in a postmenopausal woman caused by a Sertoli-Leydig cell tumor (SLCT) in which evaluation was complicated by the pattern of androgen elevation, bilateral adrenal nodules, and absence of an adnexal mass. Case: A 64-year-old female was referred for evaluation of hyperandrogenism. Hirsutism, temporal hairline regression, and unusually deep voice were noted on examination. Two total testosterone levels obtained one month apart were 146 ng/dL (2-45), and measurements of dehydroepiandrosterone sulfate (DHEAS) and androstenedione were 299 mcg/dL (12-133) and 1.84 ng/mL (0.130-0.820), respectively. Abdominal CT revealed bilateral adrenal nodules - 2 cm and - 5 Hounsfield units (HU) on the left, and 1.5 cm and 5 HU on the right - but no ovarian masses. Transvaginal ultrasonography also failed to identify a discrete ovarian mass but showed endometrial hyperplasia. Virilization, magnitude of testosterone elevation, and results of imaging were felt to be most strongly indicative of ovarian hyperthecosis, and the patient underwent laparoscopic bilateral salpingo-oophorectomy and hysterectomy. The right ovary was 2.3 cm in largest diameter and approximately 90% replaced by an orange-red mass that showed Sertoli and Leydig cells on microscopy, immunohistochemical staining for the sex cord proteins inhibin and calretinin, and presence of the Leydig cell marker melan A. It was classified as well differentiated. Additional CT imaging and robotic assisted laparoscopy confirmed a stage IA tumor. One month after surgery, hyperandrogenemia had completely resolved (total testosterone < 10 ng/dL, androstenedione 0.379 ng/mL, and DHEAS 99 mcg/dL), and changes of virilization had mostly regressed at an eight months appointment. Discussion: SLCTs are a type of sex-cord stromal ovarian tumor. They constitute < 0.5% of ovarian tumors but account for approximately 75% of testosterone-secreting ovarian masses. This patient’s case was unusual for multiple reasons: 1. Age - most SLCTs are diagnosed in the second or third decade, 2. Imaging - CT and ultrasonography usually show a solid or solid and cystic adnexal mass, and co-existing adrenal nodules are rare, likely due to typical young age of presentation, and 3. Pattern of androgen elevation - DHEAS was more than two-fold elevated, and usually < 10% of DHEA and DHEAS are produced by the ovaries. However, DHEAS fell significantly after oophorectomy. SLCTs are a potential etiology of virilization in postmenopausal women even in the absence of a detectable adnexal mass and when biochemistries and imaging raise the possibility of an adrenal source of androgen.

Intrathyroidal Branchial Cleft Cysts Presenting as Bilateral Thyroid Nodules

Introduction: Intrathyroidal brachial cleft cysts are a rare entity and are usually associated with Hashimoto’s thyroiditis. Etiology is not very clear at this point, but they are thought to arise from the ultimobranchial body remnant during embryogenesis of the gland versus originating secondary to chronic inflammation as a form of squamous metaplasia. They are a common finding in the lateral neck but not with the thyroid. We present a case of a suspicious appearing bilateral thyroid nodules which were found to branchial cleft cysts on biopsy. Clinical Case: A 56-year-old woman presented to us for evaluation of thyroid nodules. Her past medical history was pertinent for endometrial cancer status post surgery and radiation, obesity, sleep apnea, hyperlipidemia and hypothyroidism. She was diagnosed with hypothyroidism around 30 years ago and had been on Levothyroxine since then. She was recently noted to have a low TSH level on routine labs done by her primary care provider and therefore her Levothyroxine dose was adjusted. She also underwent a thyroid ultrasound due to exam findings of a palpable thyroid nodule. The ultrasound revealed a suspicious 2.2 cm hypoechoic solid nodule with irregular margins and micro-calcifications in the left mid thyroid lobe. Additionally, she was also noted to have a 0.8 cm hypoechoic nodule with irregular margins in the right mid thyroid lobe. No concerning cervical lymphadenopathy was identified. She was hence referred to us for further evaluation. She denied having compressive symptoms and did not have history of head/neck radiation or family history of thyroid cancer. Both nodules were biopsied but were interpreted as non-diagnostic with insufficient follicular cells and colloid. She underwent repeat biopsy of both nodules which again was interpreted as non-diagnostic. After discussion with patient, given her suspicious ultrasound findings and inconclusive biopsy results she was referred to endocrine surgery for surgical evaluation. Shortly after she underwent total thyroidectomy with pathology consistent with bilateral benign branchial cleft like cysts associated with adjacent thyroid follicles undergoing squamous metaplasia admixed with chronic inflammation. Conclusion: Pathogenesis of these intrathyroidal branchial cleft cysts is still unclear and not many similar cases have been reported in the literature so far. These commonly present as a painless mass but sometimes can also be an incidental finding. There are not a lot of specific details in the literature regarding imaging or pathology characteristics of these lesions therefore resulting in surgical intervention to reach a definitive diagnosis.

Occurrence of Hepatocellular Carcinoma in a 40-Year-Old Male With MEN2A Syndrome

Background: Multiple Endocrine Neoplasia Type 2A (MEN 2A) is a genetic syndrome in which the patient is susceptible to the development of: 1. medullary thyroid carcinoma, 2. pheochromocytoma, and 3. parathyroid adenomas or hyperplasia. Our objective is to report the first occurrence of hepatocellular carcinoma in a young adult male with MEN 2A syndrome without prior liver disease.Clinical Case: A 40-year-old male was screened positive for the C634R point mutation of the RET Proto-Oncogene after his sister with MEN 2A syndrome had tested positive. The patient had no history of alcohol or drug abuse. His family history was remarkable for the deaths of his mother and maternal grandmother from unknown malignancies at the ages of 35 and 45 respectively. His physical exam revealed a BP of 135/85mm Hg, BMI 26 kg/m2 and palpable bilateral thyroid nodules. Lab tests included a calcitonin of 131 pg/ml, (0.0-8.4 pg/ml), calcium 11.4 mg/dL (8.4-10.3 mg/dL), parathyroid hormone (PTH) 1765 pg/ml (12-65 pg/ml), ALK PHOS 1856 U/L (20-120 U/L), ALT 16 U/L (<39 U/L), Albumin 4.1gm/dl (3.4-5.0gm/dl), plasma normetanephrine 0.95 nmol/L (0.00- 0.89 nmol L) and urine metanephrines 291 pg/d (62-207 pg/d). A CT scan demonstrated hyperdense 12 mm right and 5 mm left adrenal nodules, both confirmed MIBG positive. Neck ultrasound showed bilateral thyroid nodules, the largest measuring 1.1 x 0.8 x 1.1 cm in the right lobe and a 3.5 x 2.2 x 2.1 cm heterogeneous mass posterior to the right thyroid lobe. The patient was prepped with doxazosin and underwent a laparoscopic right adrenalectomy then 2 months later a total thyroidectomy with neck lymph node dissection, resection of the right parathyroid tumor mass and bilateral inferior parathyroid glands. Surgical pathology confirmed the right adrenal pheochromocytoma, multifocal bilateral medullary thyroid cancer with 1 of 70 neck lymph nodes positive and a single large parathyroid adenoma. He received levothyroxine to maintain euthyroidism. Within 6 months of his surgery, calcitonin was < 2 pg/ml, CEA 2.3 U/ml (<5.0 U/ml) and ALK PHOS 44 U/L. Urine metanephrines remained mildly elevated 291 pg/d (62-207 pg/d). Serial abdominal CT imaging revealed no change of the left adrenal mass but three new bi-lobar 1-2 cm enhancing liver lesions. CT guided needle biopsies of the liver masses revealed hepatocellular cancer without evidence of cirrhosis. The patient underwent successful thermal ablation of all 3 liver lesions. Laboratory evaluation was negative for Hepatitis A, B and C. His alpha fetal protein level has remained stable in the range of 4.7 to 5.8 ng/ml (<15ng/ml).Conclusions: This is the first reported case of hepatocellular carcinoma in a patient with MEN 2A syndrome who had no predisposing liver disease, raising suspicion that his germline RET mutation contributed to his liver cancer.

Carney Complex With Endocrine Involvement Isolated to the Thyroid Gland

Abstract Introduction: Carney complex is a rare autosomal dominant disorder characterized by pigmented lesions of skin and mucosae, endocrine neoplasms or overactivity, and myxomas of the heart, skin, and other organs. Most patients have at least two affected endocrine organs at time of diagnosis. We present a case of Carney complex with endocrine involvement limited to the thyroid gland. Case: A 48-year-old female was referred for evaluation of thyroid nodules incidentally discovered on imaging for submandibular salivary gland swelling. Ultrasound evaluation of the thyroid revealed numerous, bilateral nodules that were mostly cystic or spongiform, though some had irregular borders and microcalcifications. A brother with Carney complex had been diagnosed with papillary carcinoma, and the patient decided to undergo thyroidectomy. Fortunately, no thyroid carcinoma was found on postsurgical histopathology. Initial biochemical evaluation showed no evidence of hypercortisolemia (8 AM cortisol 1.7 mcg/dL on 1 mg dexamethasone suppression test; 24-h urine cortisol 26.1 mcg [reference: 4-50]), growth hormone excess (IGF-1 190 ng/mL [reference: 52-328]), or hyperprolactinemia (prolactin 10 ng/mL [reference: 2.74-26.72]). Imaging showed no pituitary or adrenal masses. The patient underwent total hysterectomy with bilateral salpingo-oophorectomy for endometrial cancer prior to referral. She was diagnosed with Carney complex at age 19 years, and her manifestations included atrial and ventricular myxomas, intraductal adenoma of the breast, multiple skin lesions (lentigines, blue nevi, and cutaneous myxomas), and myxomas of the external auditory canals. She is in a Carney complex kindred that includes her mother, two brothers, and a niece. Discussion: Carney complex is usually caused by inactivating mutations or large deletions in the protein kinase A type I alpha regulatory subunit (PRKAR1A) gene located on chromosome 17q22-24. Most mutations are inherited in an autosomal dominant manner, though approximately 30% of cases are due to de novo mutations. In a review of 365 cases, the median age at diagnosis was 20 years. Growth hormone adenomas or somatomammotroph hyperplasia occurs in approximately 75% of patients, and most have at least one additional endocrine abnormality including multinodular goiter, primary pigmented nodular adrenocortical hyperplasia, and testicular or ovarian masses. There is an approximately 10% chance of developing well differentiated thyroid carcinoma. Treatment for Carney complex is individualized depending on the patient’s presentation and includes excision or surgical removal of myxomas, neoplasms, and skin lesions, as well as regular evaluation for cardiac myxomas and endocrine overactivity. This case of Carney complex is unusual because the only endocrinopathy is multinodular goiter.

A Case of Paraneoplastic Hypoglycemia From Squamous Cell Carcinoma of Undetermined Primary

Case: A 57 year old man with squamous cell carcinoma (SCC) of the tongue with complete response to chemoradiation was found unresponsive with a reading of “low” by a POC glucometer. He was treated with an IV dextrose bolus but had recurrent hypoglycemia requiring a continuous dextrose infusion. He was diagnosed with COVID-19 pneumonia, acute hepatitis (elevated liver enzymes), and acute kidney injury (elevated serum creatinine 1.2 mg/dL). Other labs: elevated TSH 8.44 uIU/mL, normal AM cortisol 16.4 ug/dl. A 5.1 cm mass was discovered in the left lung with bilateral nodules, biopsi revealed SCC of unclear origin (either lung or metastatic disease from prior tongue cancer). He was malnourished from prior cancer related dysphagia and nutritional supplements were added. Despite this and improvement in liver and kidney function, he had persistent hypoglycemia. He became hypoglycemic within 4-hrs while performing a 72-hr fast with labs: serum glucose 45 mg/dL, insulin < 2 uU/mL, c-peptide < 0.1 ng/mL, proinsulin < 4 pmol/L, beta hydroxybutyrate 0.17 mmol/L, IGF1 < 16 ng/mL (ref: 50 - 317), IGF2 147 ng/mL (ref: 267-616), negative hypoglycemia panel and insulin antibody. This was consistent with a paraneoplastic hypoglycemia known as non-islet cell tumor hypoglycemia (NICTH). To discontinue the dextrose infusion, he was started on prednisone 20 mg daily titrated up to 60 mg daily, intermittent tube feeds and palliative chemotherapy. With this, hypoglycemia improved, and the dextrose infusion was discontinued. Unfortunately, he had ischemic bowel perforation leading to cardiac arrest and death. Discussion: Our patient had NICTH as suggested by the 72-hr fast (non-insulin mediated hypoglycemia, IGF2/IG1 ratio > 10) and the presence of a tumor. It is mediated by tumor-produced IGF-2 causing increased glucose utilization, decreased gluconeogenesis, glycogenolysis and ketogenesis. Curiously, IGF-2 may not be elevated if the tumor produces a partially processed “big IGF-2” for which there is no commercial assay. Instead, an IGF2/IGF1 ratio close to or more 10 is indicative of NICTH. Mesenchymal and hepatic tumors are the most common cause of this rare entity with an incidence of one per million people years. A literature search showed very few reports of SCC-mediated-NICTH, with one case of esophageal SCC. Our patients’ primary tumor was undetermined (lung vs tongue) - but in either case this could be a novel association. A multidisciplinary approach is required centered around the tumor (surgery, chemotherapy, or radiation). High dose prednisone 30 to 60 mg daily can be used in the interim as it decreases IGF-2 but is not always successful. Recombinant hGH and glucagon are alternatives or can be combined with steroids. In summary IGF2/IGF1 ratio should be calculated, palliative tumor directed therapy should be initiated with prednisone and supplemental nutrition as adjuncts.

Bilateral Adrenal Adenomas Attributed to Extrapulmonary Mycobacterium Tuberculosis

Introduction: Adrenal infections are rare, with the Mycobacterium tuberculosis (MTB) being the most common causative agent in the developing world. MTB usually spreads to the adrenal glands hematogenously where it may be clinically manifested years after systemic infection. Here, we present a case of bilateral adrenal MTB infection associated with MTB peritonitis. Case Presentation: A 46-year-old male, from Ecuador, without significant medical history and no medical follow-up presented to the emergency room with a two-week history of abdominal pain, nausea, diarrhea, and significant weight loss. He denied fever, cough, or night sweats. No smoking, alcohol, or illicit drug use. He works as a construction worker without a history of sick contacts. Vital signs were stable, with abdominal distension and fluid shifting dullness on exam. Blood work revealed leucocyte count of 5.58K (4-11K), INR 1.2 (0.9–1.1), Sodium 132 mEq/L (136–145 mEq/L) with albumin 3.3 mg/dL (3.5–5.2 mg/dL), total bilirubin level, 1.3 mg/dL (0–1.2 mg/dL), and AST and alkaline phosphatase levels, 73 U/L (0–40 U/L) and 186 U/L (40–129 U/L) respectively. Computerized tomography (CT) of the abdomen showed large ascites, omental nodularity, calcified gall bladder, bilateral adrenal nodules, and multiple abdominal lymphadenopathies. Chest CT revealed right apical reticulonodular densities. A diagnostic paracentesis revealed an exudative effusion with serum ascites albumin gradient of 0.7, and negative acid fast bacilli (AFB) and adenosine deaminase enzyme. Ascitic cellular analysis was negative for malignant cells. AFB blood and sputum cultures were negative, though Quantiferon gold test was positive and a skin tuberculin test was 13x13mm. Tumor markers CA19-9, CEA, and alpha-fetoprotein came back negative. Additionally, serum aldosterone, plasma metanephrines, DHEA-S, AM Testosterone, ACTH, and morning cortisol levels were normal. The patient had a negative 1-mg dexamethasone suppression test. Positron emission tomography (PET) scan showed a hypermetabolic left adrenal mass (4.9x3.2 cm) and nodular peritoneum with no fluorodeoxyglucose (FDG) uptake in the enlarged abdominal lymph nodes. Peritoneal biopsy analysis revealed non-caseating granuloma positive for MTB. The adrenal biopsy was not performed given the extensive intra-abdominal disease. The patient was started on anti-MTB treatment (Isoniazid, rifampicin, pyrazinamide, and ethambutol) with significant clinical improvement and a slight decrease in the adrenal masses following abdominal imaging. Conclusion: Extrapulmonary MTB should be part of a differential diagnosis for bilateral adrenal masses. Adrenal glands could be infected by a variety of pathogenic microorganisms either by direct contact or hematogenous dissemination. A high index of suspicion is required for the diagnosis of MTB in patients with atypical presentation.

Recurrent Pheochromocytoma, as Component of Multiple Endocrine Neoplasia

Background: Pheochromocytoma is a rare neuroendocrine tumor from the adrenal medulla’s chromaffin cells that secrete catecholamines. The mainstay of treatment is surgery. Although rare, it has a recurrence rate of 6.5-16.5% even after adequate surgical removal with a notable increase in prevalence among genetic syndromes, extra-adrenal tumors, larger tumor size, and younger age of diagnosis. Case: A 23-year-old Filipino male with no known familial disease presented with episodic headache, palpitations, diaphoresis, and resistant hypertension. Two masses in the left adrenal gland, with the larger one measuring 6.0cm x 5.0cm x 3.0cm, were surgically removed. Histologic examination revealed pheochromocytoma. Post-operatively, there was the normalization of urinary metanephrines and the resolution of the signs and symptoms. He was lost to follow-up and returned five years later with an abdominal ultrasound demonstrating a right adrenal mass. He had no accompanying signs and symptoms; the physical examination was unremarkable. On workup, biochemical testing revealed two 24-hour urinary metanephrine levels were markedly elevated, 14.49 and 19.97 (NV:0-1mg/24 hours). Calcitonin: 644 (NV:0-18pg/ml) and carcinoembryonic antigen (CEA): 23.52 (NV:<5ng/ml) were also elevated. Mild hypercalcemia was noted with elevated intact PTH 101.74 (NV:0-65pg/ml). Parathyroid scintigraphy was normal. The neck ultrasound showed multiple bilateral thyroid nodules, with the largest measuring 1.2cmx0.9cm (TIRADS IV). The abdominal CT scan showed two well-defined, homogenous right adrenal masses, with the largest measuring 6.3cm x 5.6cm x 7.4cm. He underwent right adrenalectomy, and histopathology showed pheochromocytoma with Pheochromocytoma of the Adrenal Scale Score (PASS) of 3. One month later, he underwent total thyroidectomy with neck dissection and inferior parathyroid gland resection. Histopathology confirmed medullary thyroid cancer with nodal metastasis and parathyroid adenoma. The patient recovered well without complications. Biochemical tests normalized eight weeks post-surgery. The presence of synchronous recurrent pheochromocytoma, medullary thyroid cancer (MTC), and primary hyperparathyroidism is consistent with multiple endocrine neoplasia 2A (MEN2A) syndrome. Conclusion: Lifelong follow-up is essential in patients treated for pheochromocytoma despite the complete removal of the adrenal masses due to recurrence risk. Recurrence should likewise raise the suspicion of MEN2, a genetic syndrome. In addition, the pheochromocytoma has malignant characteristics, and the MTC has metastases to the cervical lymph nodes. Early detection and prompt intervention are essential for the treatment of the disease.

Thyroid Angiosarcoma Complicated by Neck Hematoma

Abstract Background: Primary angiosarcoma of the thyroid is a rare, aggressive thyroid malignancy most typically found in the Alpine regions of Europe. We present a case of non-Alpine thyroid angiosarcoma complicated by recurrent surgical bed hematoma. Case: An 81-year-old Albanian man presented with two months of dyspnea and hemoptysis and was found to have a large thyroid mass, multiple subcentimeter pulmonary nodules, and a left pleural effusion seen on CTA of the chest. He had a suppressed TSH &amp;lt; 0.008 uIU/mL (n 0.400-4.200 uIU/mL) on presentation with a normal free T4 (1.36 ng/dL; n 0.80-1.50 ng/dL) and total T3 (107 ng/dL; n 87-178 ng/dL). Labs from 3 years prior were consistent with prior subclinical hyperthyroidism: TSH 0.28 uIU/mL, free T4 1.35 ng/dL, and free T3 3.98 pg/mL (n 2-4.4 pg/mL). A thyroid ultrasound was performed and showed multiple bilateral thyroid nodules, the largest of which was 6.0 x 7.8 x 5.4 cm in the right lower pole. He had no compressive symptoms and was clinically euthyroid. FNA of the nodule was non-diagnostic and cytology of the pleural fluid was negative for malignancy. He underwent a bronchoscopy which showed blood clots without endobronchial lesions, VATS with pleural biopsy, and right hemithyroidectomy. Pathology showed high grade epithelioid malignancy arranged in solid, variably discohesive nests and sheets, associated with vague vasoformative features and hemorrhage. Immunostains were diffusely and strongly positive for ERG as well as CD31 and AE1/3, but negative for PAX-8, TTF-1, and thyroglobulin, supporting a diagnosis of angiosarcoma. The remainder of the thyroid tissue was non-neoplastic with multinodular hyperplasia. After initial discharge, he re-presented on post-op day 10 with bleeding from the surgical site. CT of the neck showed extensive hematoma (10.3 x 5.0 x 8.7 cm) and he was taken back to the OR for evacuation. Residual tumor tissue found along the R carotid artery was determined to be the culprit. Over the next month the patient remained admitted for supportive transfusions, and palliative radiation to the pulmonary nodules and the residual tumor was initiated. His hospitalization was complicated by a proximal lower extremity DVT, which was treated with an IVC filter. Repeat chest imaging at six weeks showed new and progressive pulmonary nodules. Upon completion of 3 weeks of RT the patient was discharged debilitated, fatigued, and using supplemental oxygen. His family elected to pursue hospice care. Conclusion: This case represents a rare, aggressive malignancy complicated by extrathyroidal extension and recurrent hematoma resulting in severe morbidity and precluding further systemic interventions. These highly vascular tumors likely present an elevated risk for postoperative hematoma which clinicians should recognize.

A Rare Case of a Toxic Thyroid Nodule Found in a Hypothyroid Patient on Levothyroxine Therapy

Introduction: A hyperfunctional thyroid nodule can lead to symptoms of overt or subclinical hyperthyroidism but the association between a hyperfunctional thyroid nodule and hypothyroidism has not been well reported. We present a patient with a prior history of hypothyroidism previously controlled on Levothyroxine who later presented with an enlarging hot nodule. Case Presentation: A 62-year-old female with a history of factor V Leiden, hypothyroidism on levothyroxine therapy, and a meningioma presented to an outpatient clinic with complaints of fatigue, constipation, and 37-pound weight loss in one year. She was diagnosed with hypothyroidism 7 years ago after delivering her third child, but the underlying cause of her disease was unknown. She began taking levothyroxine 50mcg every morning after her diagnosis. She reported compliance and proper pill taking technique. Physical examination revealed a palpable thyroid nodule. The patient had a previous work up for thyroid nodules with a thyroid uptake and scan a few years prior, which showed a 1.42 x 0.96 x 1.87 cm hot nodule at the right middle lobe with a 24-hour uptake of 15.3%. The patient was asymptomatic at that time and thyroid function tests were within normal limits. She was instructed to continue taking levothyroxine. Repeat RAI Uptake scan at the time of her presentation to our office again showed the right middle lobe hot thyroid nodule with an increased 24-hour uptake of 27.5%. Ultrasound showed bilateral thyroid nodules and a hypervascular solid nodule measuring 2.28 x 1.27 x 1.9 cm that has increased in size. Lab work at this visit revealed a TSH of 0.329 uIu/mL, and free T4 of 1.25 ng/dL. Due to her low TSH and clinical presentation, the levothyroxine was discontinued. Anti-thyroid peroxidase antibodies were obtained to assess for Hashimoto’s Thyroiditis but were found to be normal. The patient was later referred to an endocrine surgeon for a total thyroidectomy. Conclusion: Although uncommon, hyperfunctional nodules in hypothyroid patients can create a confusing clinical picture with overlapping symptoms of underactive and overactive thyroid disease. It has been reported that patients with Hashimoto’s Thyroiditis can have hot nodules and coexisting hypothyroidism but the prevalence of hyperfunctional nodules in hypothyroid patients without Hashimoto’s Thyroiditis, as in this case, is not well-documented. Patients with hypothyroidism are treated with Levothyroxine but if coexisting hyperfunctional nodules are not detected, the patient may develop thyrotoxicosis. Clinicians should be aware of this rare but potentially life-threatening clinical condition.

The Unusual Case of a Rapidly Enlarging Thyroid Gland in a Patient With Pendred Syndrome

Pendred syndrome is a genetic condition that is characterized by sensorineural hearing loss, abnormalities of the vestibular system, and goiter. In patients with Pendred syndrome, goiter tends to develop in late childhood or early adulthood and the literature details a progressive enlargement of goiter in these individuals. Here we report the case of a 26 year old female with Pendred syndrome and congenital deafness who presented with a rapidly enlarging thyroid gland over 1 week with associated symptoms of dysphagia, dyspnea, insomnia, and diaphoresis. Thyroid function tests at the time showed no abnormalities. Diagnostic thyroid ultrasound was performed and showed enlarged, multinodular goiter and bilateral thyroid nodules measuring 1.2 cm and 1.1 cm in the right and left thyroid lobe, respectively, with TI-RADS 2 classification. The patient had a thyroid core biopsy performed showing benign appearing thyroid follicles without any evidence of malignancy. After approximately one month following the initial presentation, the patient reported resolution of her goiter and associated symptoms without intervention. To our knowledge, this is the first case in the literature detailing a rapidly enlarging goiter in a patient with Pendred Syndrome, with subsequent resolution of signs and symptoms.

Never Forget the Family History: MEN2A Syndrome Presenting as Metastatic Medullary Thyroid Cancer and Bilateral Pheochromocytoma

Abstract Introduction: MEN 2A is an autosomal dominant hereditary syndrome considered part of the medullary thyroid carcinoma (MTC) syndromes. This is characterized by MTC, pheochromocytoma, and parathyroid hyperplasia or adenomas causing primary hyperparathyroidism (PHPT). Clinical Case: A 34 year old female was referred to our clinic for multi-nodular goiter diagnosed during routine gynecologic evaluation. A thyroid ultrasound revealed a heterogeneous right thyroid lobe with a hypoechoic 2.5 cm nodule, associated macro calcifications and increased vascularity; and a left nodule measuring 2.3 cm with the same characteristics. Bilateral thyroid nodule biopsies were performed, resulting in MTC confirmed by positive calcitonin staining. Pre-operative studies revealed serum calcitonin and carcinoembryonic antigen (CEA), both of which are considered serologic markers of MTC activity, at 4,340 pg/ml (n &amp;lt;= 5) and 276.2 ng/mL (n &amp;lt;= 2.5 in non-smokers) respectively. The patient reported father with history of unspecified thyroid cancer, and paternal uncle with history of pheochromocytoma with a p.Cys634Trp mutation in RET proto-oncogene. Due to her family history, pre-operative screening for primary hyperparathyroidism (PHPT) resulted in a calcium 10 mg/dL (n 8.6-10.2), PTH 34 pg/mL (n 14-64). Additionally, screening for pheocromocytoma revealed an elevated 24 hour urine metanephrines of 2,276 (n &amp;lt;= 49-290) ug/24h, plasma metanephrines, including fractionated metanephrine (MN) at 163 (n &amp;lt;= 57) pg/ml, fractionated nor-metanephrine (NMN) at 182 (n &amp;lt;= 148) pg/ml, and total, Free (MN+NMN) metanephrines at 345 (n &amp;lt;= 205) pg/ml. CT abdomen revealed bilateral adrenal nodules, right measuring 1.4 x 3.3 cm and left 2.4 x 3.3 cm. The patient underwent posterior retroperitoneoscopic adrenalectomy with cortex sparing prior to thyroidectomy. Adrenal pathology resulted in bilateral pheochromocytoma with peri-adrenal adipose tissue microscopic involvement, and positive synaptophysin and S-100 stain. Subsequently, she underwent total thyroidectomy with extensive cervical lymph node resection, with pathology resulting in MTC with lymph node metastasis, involving 5/18 cervical lymph nodes. Post-operative labs revealed serum calcitonin &amp;lt;= 2 pg/ml, CEA 26.8 ng/mL, MN &amp;lt; 25 pg/ml, NMN 102 pg/ml, and MN+NMN of 102 pg/ml, which suggested initial surgical success. Post-operative genetic test evaluation revealed abnormal RET oncogene testing compatible with MEN 2A, variant 1: c.1902C&amp;gt;G (p.Cys634Trp). Conclusion: This case illustrates that patients presenting with MTC and reporting family history of thyroid cancer should be screened for familial MTC syndrome. Patients with RET mutation should be screened for pheochromocytoma prior to surgery for MTC to prevent life-threatening hypertensive crisis.

Unlikely Coexistence of Sporadic Pheochromocytoma and Bilateral Macronodular Adrenal Hyperplasia: A Challenge to Manage

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.

Papillary Thyroid Carcinoma Within Thyroglossal Duct Cyst

A 55-year-old female with medical history of hypothyroidism and fibrocystic disease of the breast presented with complains of a painful anterior neck mass, difficulty swallowing and hoarseness of the voice. Symptoms had progressed over a period of 5 months. CT neck with contrast indicated the presence of an ectopic thyroid tissue anterior to the thyroid cartilage measuring approximately 1.7 x 1.2 x 3.1 cm, with indistinct inferior margins and internal calcifications. The hyoid bone or thyroid cartilage had no irregularities. The thyroid gland itself was unremarkable except for small complex thyroid nodules in both lobes. No masses within the pharynx or larynx were noted.Family history was significant for lymphoma in her father.On physical exam, a hard, mobile right anterior neck mass was appreciated. Labs showed normal TSH of 1.05 uIU/mL and normal free T4 of 1.2 ng/dL.Further evaluation with a dedicated neck US showed a right submandibular mass, superior to the thyroid, lobulated and heterogeneous measuring 2.0 x 1.0 x 2.3 cm with multiple areas of calcifications and internal Doppler flow. The thyroid gland had normal size and texture with bilateral sub centimeter non-concerning nodules.After ENT evaluation and an unremarkable flexible fiberoptic nasolaryngoscope, patient underwent surgical excisional biopsy of the neck mass. Pathology was consistent with thyroglossal duct cyst with the presence of thyroid follicles. An incidental finding of a 0.9 cm papillary microcarcinoma was noted, which was encapsulated with focal extracapsular follicular structures showing papillary nuclear features with no perineural or lymphovascular invasion. The tumor cells were immunoreactive for TTF-1 and PAX8.Development of papillary thyroid cancer within the thyroglossal duct cyst is a rare event, reportedly occurring in 1% of thyroglossal duct cysts. There are no well-established management guidelines.Current management strategies consist of monitoring with serial neck ultrasound versus total thyroidectomy with consideration of postsurgical I-131 treatment, based on pathology results. Our patient opted for undergoing total thyroidectomy.

Bilateral Subepidermal Calcified Nodules of the Upper Eyelid

Bilateral Subepidermal Calcified Nodules of the Upper Eyelid

All that is Miliary is not tuberculosis

Miliary pattern on radiographs are attributed always to tuberculosis even though the differential diagnoses of miliary pattern is very wide. This pattern is most commonly caused by infectious diseases and rarely by malignancies. Primary lung cancers presenting with miliary shadows is extremely rare. Here we report a case of 50-year old female, presenting with 15 days of symptoms and CXR PA view showing bilateral diffuse miliary nodules. HRCT Chest confirmed the miliary pattern and also showed a mass in left lower lobe. Microbiological tests for tuberculosis and fungal infections were negative. CECT Chest gave impression of left lower lobe suspected malignant lung mass with pulmonary metastasis. Malignancy was confirmed by CT guided FNAC as Adenocarcinoma lung. PET scan didnot reveal metastasis in other organs. CONCLUSION : Miliary pattern does not always indicate tuberculosis and other possibilities should be evaluated.

IIMAGING OF PRIMARY ALDOSTERONISM IN YOUNG PATIENTS FROM A LARGE INTERNATIONAL STUDY (AVIS-2-YOUNG)

Objective: Purpose The Endocrine Society guidelines suggested skipping adrenal vein sampling (AVS) when referring for surgery young PA patients with a unilateral adrenal nodule and a contralateral normally appearing gland at imaging, but this was based on a limited set of cases. Hence, we sought to determining if imaging provided an accurate identification of unilateral PA. Materials and Methods: We examined the large cohort of patients ?45 years-old recruited in the AVIS-2-Young study. Biochemical cure of PA after unilateral adrenalectomy was used as the final diagnosis to assess imaging diagnostic accuracy. Results: Among the 1625 AVIS-2 patients those ?45, 40 and 35 years-old were 29.0%, 15.5% and 6.1%, respectively. In the same age cohorts, a unilateral adrenal nodule was found in 53.2%, 57.3% and 47.3%; 42.6%, 38.5% and 50.9%, respectively, showed no nodules and 4.2%, 4.2% and 1.8% bilateral nodules. In those with a unilateral nodule, the culprit adrenal was identified in 81.4%, 84.1%, and 92.3% of the patients. Youden index analysis identified ? 38 years as the best cut-off for unilateral PA identification; by restricting the analysis to those with a nodule size to &gt; 10 mm, the overall concordance was 94.0%. However, bilateral or no nodules were detected at imaging in &gt; 37% of the patients with a final diagnosis of unilateral PA in all age cohorts. Conclusion: Referring PA patients ?45, 40 and 35 years-old based on a unilateral nodule at imaging carried a likelihood of wrong/inappropriate surgery in 18.6%, 15.8% and 7.7%, respectively. This error rate can be minimized to 6.0% by selecting patients ?38 years with a nodule &gt; 10 mm. However, in these age cohorts up to 1/3 of the patients, who had unilateral surgically curable PA were not detected with imaging.

Rituximab for refractory necrotizing scleritis and peripheral ulcerative keratitis secondary to antineutrophil cytoplasmic antibody-negative granulomatosis with polyangiitis

A 52-year-old woman was diagnosed with bilateral necrotizing scleritis (NS) and peripheral ulcerative keratitis secondary to the antineutrophil cytoplasmic antibody (ANCA)-negative granulomatosis with polyangiitis (GPA) as evidenced by increased erythrocyte sedimentation rate, bilateral multiple cavitation lung nodules, and persistent microscopic hematuria. Infective workup and autoimmune tests were negative including the ANCA test. She received multiple courses of high dose intravenous methylprednisolone, intravenous cyclophosphamide, and oral methotrexate. Multiple tectonic patching operations were performed. Despite all the treatment, the disease continued to progress. Eventually, few doses of rituximab were given and the disease was stable for at least a year without any reactivation.

Histological Investigation of Pneumonia in Domestic Ducks (Anas platyrhynchos domesticus) in Basrah Province, Iraq

The current study was performed to the histological features of pneumonia in domestic ducks in Basra province of Iraq. The diseased ducks were diagnosed based on clinical manifestations, gross and microscopical lesions as well to histochemical technique. The necropsy findings were characterized by presence white to yellowish bilateral solid uniformed nodules in the parietal surface of the right and left lungs as well to an obvious lesion of red to gray hepatization extend bilaterally in the both lung; however, additionally, both lungs showed bilateral severe congestion mostly in the middle to lower parts with scattered nodules. The microscopic picture indicate a severe interstitial hemorrhage, as well to infiltration of inflammatory cells mainly in the bronchi and interstitial pulmonary tissues revealing to bronchopneumonia; in addition to severe fibrinous exudate that contains a fibrin associated with inflammatory cells infiltration, as well to peri-bronchial inflammatory cells infiltration. The histochemical results showed formation of thick fibrous connective tissue infiltrated in pulmonary interstitial parenchyma and in peri bronchial tissue revealed to diffuse interstitial pulmonary as well to severe interstitial infiltration of mucoid like substances in the pulmonary parenchyma and in the peri-bronchial tissue. It has been concluded that the typical histological features of pneumonia of domestic ducks characterized by severe stages of pulmonary congestion, red and gray hepatization that may overlapped in the complicated cases.

Simultaneous Uniportal video-assisted thoracic surgery of bilateral pulmonary nodules

BackgroundSurgical resection is an appropriate treatment option for synchronous bilateral pulmonary nodules with ground-glass opacities. The applicability of simultaneous uniportal video-assisted thoracic surgery is not fully understood. We evaluated the feasibility and safety of performing such surgeries at our hospital.MethodsClinical data of 35 patients who underwent simultaneous bilateral pulmonary resection with uniportal video-assisted thoracic surgery at our hospital were reviewed retrospectively.ResultsSimultaneous bilateral pulmonary resection with uniportal video-assisted thoracic surgery was performed for 35 patients (15 men, 20 women); 97 nodules were operated on, and the average nodule diameter was 11.4 mm (range, 1–38 mm). Computerized tomography showed that most nodules had ground-glass opacity (52/97, 53.6%); solid nodules (24/97, 24.7%) and nodules with mixed ground-glass opacity (21/97, 21.7%) were noted. Surgical resection included lobar-sublobar resection (11/35, 31.4%) and sublobar-sublobar resection (24/35, 68.6%). Wound infection and postoperative 30-day mortality were not observed. Pneumonia was the major postoperative complication, with a higher incidence in the lobar-sublobar group (6/10, 60%) than in the sublobar-sublobar group (4/25, 16%; P = 0.016). Pneumonia did not correlate with operative time (mean, 262.3 ± 108.1 vs. 261.9 ± 87.5 min, P = 0.991), duration of chest drainage (mean, 7.0 ± 4.0 vs 5.4 ± 2.1 days, P = 0.124), and postoperative hospital stay (mean, 10.2 ± 3.6 vs 10.2 ± 6.4 days, P = 0.978). The mean follow-up time was 8 (range, 3–22) months. Recurrence of primary lung cancer or mortality was not noted at the final follow-up.ConclusionsSimultaneous bilateral pulmonary resection with uniportal video-assisted thoracic surgery is feasible and safe for appropriate patients. Simultaneous lobar-sublobar pulmonary resection for bilateral nodules can increase the risk of developing pneumonia.

A year of hepatocellular carcinoma at a glance. Demographics, biochemical and radiological characteristics and treatment modalities from a specialized facility of Pakistan.

To analyse the relation of demographics of hepatocellular carcinoma with the aetiology in order to analyse tumour characteristics in relation to anti-viral therapy and the presence of viral-deoxyribonucleic acid/ribonucleic acid, and the treatment modalities offered. The cross-sectional study was conducted at the Department of Gastroenterology, Pak Emirates Military Hospital, Rawalpindi, Pakistan, from January 1 to December 31, 2019, and comprised patients aged 18-70 years with diagnosed hepatocellular carcinoma. Demographic variables, biochemical analysis, including liver profile and stage of cirrhosis, viral-status, tumour staging and the treatment modalities offered were noted. Of the 195 patients, 148(76%) were males and 47(24%) were females. The overall mean age was 59.8±8.9 years. There were 187(96%) patients with cirrhosis, 183(94%) corresponded to viral hepatocellular carcinoma, 160(82%) had hepatitis C, 18(9%) had hepatitis B and 6(3%) had co-infection. Platelets and alanine transaminase had a significant relation across aetiological groups (p<0.05). The presence of viral polymerase chain reaction had a significant impact on tumour aggressiveness (p<0.05). And, 62(32%) patients were amenable to curative treatment. Viral infection was found to be the main cause of rising prevalence of hepatocellular carcinoma. Treatment modalities were found to be expensive, and expertise was lacking.