scholarly journals SAT-370 Novel CASR Gene Mutation as a Cause of Familial Isolated Primary Hyperparathyroidism

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Andrea K Juneau ◽  
Adwoa Opoku-Boateng ◽  
Gabriel Ikponmosa Uwaifo
Keyword(s):  
Family History ◽  
Primary Hyperparathyroidism ◽  
Hospital Admissions ◽  
Novel Mutation ◽  
Pituitary Tumors ◽  
Loss Of Function ◽  
Casr Gene ◽  
Gene Testing ◽  
Calcium Sensing ◽  
History Of

Abstract BACKGROUND: Primary hyperparathyroidism (pHT) is one of the most common causes of hypercalcemia. About 10% of these patients have a familial cause of which MEN and the hyperparathyroid-jaw tumor syndrome (HJTs) are most common. Familial hypocalciuric hypercalcemia (FHH) due to loss of function mutations of the calcium sensing receptor (CASR) gene is an important familial mimic of this that needs to be distinguished. Beyond this are still a group of patients with familial isolated primary hyperparathyroidism (FIpHT). Recognition of this entity is important because of the different prognostic and surgical treatment strategy for their management compared to regular sporadic pHT. Clinical Case: A 58 yr old postmenopausal lady on topical HRT was referred for thyroid nodular disease. Her initial lab tests showed primary hyperparathyroidism with mild hypercalcemia. Her initial neck sonogram showed multiple benign appearing nodules that did not warrant biopsy. There was a history of hypothyroidism in her mother and thyroid cancer in a maternal cousin. In addition, her father and two sons have history of hypercalcemia that required repeated hospital admissions for treatment. Her two daughters to date have had no hypercalcemia, nephrolithiasis nor thyroid problems. There was no family history of jaw, renal nor brain or pituitary tumors and no history of severe dyspeptic disease nor familial cancers. She had hypercalciuria, normal bone density and non-obstructive nephrolithiasis. MEN-1 gene testing was normal. Parathyroid scan suggested a possible right sided parathyroid lesion and she had elective parathyroidectomy of an ectopic right parathyroid that was hypercellular on histology. The intra-operative PTH dropped following the lesion extraction by ~ 51%. Post operatively the patient’s mild pHT and hypercalcemia persists but imaging studies have been unrevealing. Further genetic testing for other possible etiologies of familial pHT were -ve for HJTs but revealed a novel somatic mutation of the CASR gene; c.1868G>A (p.Gly623Asp) whose present significance is unclear. This variant has been described in one family with FHH but In silico predictive analyses of the mutation suggests a possible deleterious effect. Given her known family history of symptomatic hypercalcemia this novel mutation appears to be a hitherto unrecognized cause for FIpHT. The patient is presently being conservatively managed and monitored. Conclusion: While familial pHT is relatively uncommon its recognition is important as it can inform planned surgical intervention and expected prognosis for anticipated cure. While MEN and HJTs are the most common etiologies for familial pHT other possibilities need to considered when the history suggests possible FIpHT and our case highlights a novel CASR mutation as diagnostic consideration.

scholarly journals SAT-351 A Novel Mutation in the Calcium-Sensing Receptor Gene Presenting in a Kindred as Autosomal Dominant Familial Hypocalciuric Hypercalcemia

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Jordan Bushman ◽  
Ajaz Banka
Keyword(s):  
Genetic Analysis ◽  
Novel Mutation ◽  
Receptor Gene ◽  
Family Members ◽  
Heterozygous Mutation ◽  
Familial Hypocalciuric Hypercalcemia ◽  
Loss Of Function ◽  
Calcium Sensing Receptor ◽  
Casr Gene ◽  
Calcium Sensing

Abstract Rationale: Familial hypocalciuric hypercalcemia (FHH) is a benign cause of hypercalcemia. The majority of cases result from an inactivating mutation in the calcium-sensing receptor (CaSR). While affected patients are usually asymptomatic and require no treatment, this condition may go unrecognized and inappropriate parathyroidectomy for presumed primary hyperparathyroidism could be performed. Over 130 mutations in the CaSR gene have been reported and novel variants continue to emerge. Methods: The initial patient was a 49 year-old female who presented with mild hypercalcemia, elevated PTH and undetectable urine calcium. She reported several of her family members had elevated calcium levels. Given high clinical suspicion for FHH genetic analysis was performed. Results: Sequencing of the CaSR gene revealed a point mutation at c.1744T>A which resulted in p.Cys582Ser in exon 7. This cystine residue is highly conserved and predictive algorithms suggest this variant is likely disruptive leading to heterozygous loss of function in the CaSR. The patient’s 26 year-old daughter was tested and found to have the same mutation. Conclusion: We report the identification of a novel heterozygous mutation in the CaSR gene manifesting as FHH in a family of Iraqi decent. Additional family members are currently undergoing genetic analysis which will be included at the time of presentation.

scholarly journals Familial Hypocalciuric Hypercalcemia in an Index Male: Grey Zones of the Differential Diagnosis From Primary Hyperparathyroidism in a 13-Year Clinical Follow up

2020 ◽  
pp. S321-S328
Author(s):  
K. ZAJÍČKOVÁ ◽  
M. DVOŘÁKOVÁ ◽  
J. MORAVCOVÁ ◽  
J. VČELÁK ◽  
D. GOLTZMAN
Keyword(s):  
Differential Diagnosis ◽  
Family History ◽  
Primary Hyperparathyroidism ◽  
Familial Hypocalciuric Hypercalcemia ◽  
Clearance Ratio ◽  
Japanese Family ◽  
Casr Gene ◽  
History Of ◽  
Inactivating Mutation

Familial hypocalciuric hypercalcemia (FHH) type 1, caused by a heterozygous inactivating mutation of the gene encoding the calcium-sensing receptor (CaSR), is characterized by mild to moderate hypercalcemia, hypocalciuria and inappropriately normal or elevated parathyroid hormone (PTH). FHH must be differentiated from primary hyperparathyroidism (PHPT) because parathyroidectomy is ineffective in the former. Herein, we report a 39-year-old male patient with a 13-year history of asymptomatic PTH-dependent hypercalcemia (mean calcium of 2.88 mmol/l; reference range 2.15-2.55 mmol/l) and calcium-to-creatinine clearance ratio (Ca/Cr) ranging from 0.007 to 0.0198, which is consistent with either FHH or PHPT. Although a family history of hypercalcemia was negative, and PET-CT with fluorocholine was suggestive of a parathyroid adenoma, genetic analysis of the CaSR gene identified a heterozygous inactivating mutation NM_000388.4:c.1670G>A p. (Gly557Glu) in exon 6 and a polymorphism NM_000388.4:c.1192G>A p. (Asp398Asn) in exon 4. The G557E mutation has been previously reported in a Japanese family in which all family members with the mutation had Ca/Cr below 0.01 consistent with FHH. The biochemical profile of FHH and PHPT may overlap. Our FHH patient with a G557E CaSR mutation illustrates that the differential diagnosis can be difficult in an index case with no family history, (false) positive parathyroid imaging and higher calciuria than expected for FHH. Calcium intake, vitamin D status and bone resorption might have contributed to the Ca/Cr variations over a 13-year clinical follow up. This case thus emphasizes the irreplaceable role of genetic testing of the CaSR gene when clinical evaluation is inconclusive.

scholarly journals Posterior Fossa Arachnoid Cyst Masking a Delayed Diagnosis of Hyperparathyroidism in a Child

2012 ◽  
Vol 2012 ◽  
pp. 1-4
Author(s):  
B. Dhamija ◽  
D. Kombogiorgas ◽  
I. Hussain ◽  
G. A. Solanki
Keyword(s):  
Differential Diagnosis ◽  
Primary Hyperparathyroidism ◽  
Posterior Fossa ◽  
Arachnoid Cyst ◽  
Hospital Admissions ◽  
Delayed Diagnosis ◽  
Visual Disturbance ◽  
Organ Damage ◽  
Presenting Symptoms ◽  
History Of

Background. Primary hyperparathyroidism in childhood is a very rare entity, often being diagnosed late after the onset of its presenting symptoms. It most commonly affects patients in their fourth decade of life and beyond. The inclusion of primary hyperparathyroidism in the differential diagnosis is necessary when evaluating patients presenting with nonspecific symptoms such as polyuria, fatigue, weight loss, abdominal pain, nausea, and vomiting.Methods. We report the case of an eleven-year-old girl presenting with three years history of headaches, visual disturbance, along with episodes of emotional lability. Neuroimaging confirmed a large posterior fossa arachnoid cyst. It was decided to manage this lesion conservatively with surveillance. Only after further hospital admissions with recurrent loss of consciousness, dizziness, and nausea to add to her already existing symptoms, a full biochemical and endocrine assessment was performed to look for more specific causes for her presentation. These pointed to a diagnosis of primary hyperparathyroidism.Conclusions. The inclusion of primary hyperparathyroidism in the differential diagnosis should be considered when evaluating paediatric patients presenting with nonspecific (neurological, gastrointestinal, and renal) symptoms in order to establish a prompt diagnosis of the disorder and to avoid severe complications of prolonged hypercalcaemia and end-organ damage.

Atopic Dermatitis: Case Series of Individualized Homoeopathic Treatment

2021 ◽  
Vol 11 (11) ◽  
pp. 115-123
Author(s):  
Mousumi Das
Keyword(s):  
Atopic Dermatitis ◽  
Family History ◽  
Case Series ◽  
Calcineurin Inhibitors ◽  
Loss Of Function ◽  
Key Words Atopic Dermatitis ◽  
Topical Calcineurin Inhibitors ◽  
History Of ◽  
Allergic Disorders ◽  
Positive Results

Atopic dermatitis is a common, chronic, intensely pruritic, relapsing inflammatory skin disease that affects both children and adults. Atopic dermatitis is often the originating of a series of allergic disorders, mentioned as the "atopic march".There are numerous risk factors correlated with AD development. However, only two have always been related, and they are (1) family history of atopy and (2) loss of function mutations in the FLG gene. Topical anti-inflammatory therapy with topical corticosteroids or topical calcineurin inhibitors treatment are available in conventional therapy but sometimes it has been reported that patients are also benefited from Homoeopathic treatment. Four patients who presented at the outpatient department at National Institute of Homoeopathy, Saltlake, Kolkata with Atopic dermatitis and a family history of asthma, allergic rhinitis were treated with constitutional homoeopathic medicine. Details of consultations, treatment and assessment are summarized. A constitutional treatment thus eliminates the symptoms locally and internally as well as long-lasting relief from complaints. Common remedies include Mercuris Solubilis, Sulphur. This case series shows positive results of homoeopathy in the treatment of Atopic dermatitis. Key words: Atopic dermatitis, Family history, Individualized Homoeopathic treatment, Case series, repertorisation.

scholarly journals Gender-related differences in MEN1 lesion occurrence and diagnosis: a cohort study of 734 cases from the Groupe d'étude des Tumeurs Endocrines

2011 ◽  
Vol 165 (1) ◽  
pp. 97-105 ◽  
Author(s):  
P Goudet ◽  
C Bonithon-Kopp ◽  
A Murat ◽  
P Ruszniewski ◽  
P Niccoli ◽  
...  
Keyword(s):  
Family History ◽  
Pituitary Tumor ◽  
Disease Gene ◽  
Pituitary Tumors ◽  
Pancreatic Tumors ◽  
History Of ◽  
Tumeurs Endocrines ◽  
Males And Females ◽  
The Impact

ContextMultiple endocrine neoplasia type 1 (MEN1) disease is an autosomal dominant syndrome that is believed to equally affect men and women. This assumption has never been confirmed.ObjectiveThe aims of this study were to evaluate the impact of gender on the prevalence of MEN1 lesions, on their lifetime probability of occurrence, and on the diagnosis of MEN1.DesignData regarding a study of 734 cases of MEN1 from the multicenter ‘Groupe d'étude des Tumeurs Endocrines’ were analyzed.ResultsThere were 57.8% females. The prevalence and probability of pancreatic tumors were higher in males than in females (P=0.06, P=0.0004). This difference was due to gastrinomas. The prevalence and probability of developing pituitary tumors were significantly greater in females (P<0.001, P<0.0001). Thymic tumors were exclusively found in men. There were no significant gender differences in the prevalence and the probability of developing hyperparathyroidism, or adrenal and bronchial tumors, or in the proportion of positive genetic tests. A family history of MEN1 was more frequently found in men than in women at the time of diagnosis (P=0.02). In the case of pituitary tumor, the proportion of patients diagnosed with MEN1 at the time of the first lesion was lower in women (44.2%) than in men (67.3%).ConclusionThe phenotype expression of the MEN1 disease gene was different in males and females. In female patients, the possibility of MEN1 is not sufficiently taken into account. Any patient presenting a lesion that belongs to the MEN1 spectrum, such as a pituitary tumor, should be closely questioned about their family history and should be tested for hypercalcemia.

scholarly journals SAT-353 Familial Hyperparathyroidism - Due to a Rare Genetic Mutation

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Adeyinka Taiwo ◽  
Joseph Stephen Dillon ◽  
Jennifer Stinson
Keyword(s):  
Family History ◽  
Primary Hyperparathyroidism ◽  
Parathyroid Adenoma ◽  
Gene Mutation ◽  
Parathyroid Tissue ◽  
Clinical Manifestations ◽  
Young Age ◽  
Parathyroid Cancer ◽  
History Of ◽  
Familial Hyperparathyroidism

Abstract Introduction: Hyperparathyroidism occurs most commonly in middle age patients, predominantly in women. It can be caused by parathyroid adenoma, hyperplasia or parathyroid carcinoma. Genetic predisposition can be found in about 10% of primary hyperparathyroidism due to certain gene mutations. This case emphasizes the importance of taking a detailed family history when patients present with hyperparathyroidism at a young age, so that familial hyperparathyroidism, if present, can be detected and relatives screened. Clinical case: A 26 y.o. male presented with symptoms of fatigue and polydipsia for several years. He was noted to have a serum calcium of 12.4 mg/dL(8.5–10.5), with parathyroid hormone of 213 pg/ml (15–65). He denied any history of kidney stones, fractures and no palpable neck masses. The patient’s family history was significant for his paternal half-sister who had parathyroidectomy for hyperparathyroidism at 20yrs old and paternal grandmother died of parathyroid cancer in her 50s. The patient’s father died of pancreatic cancer at 41yrs old. A neck ultrasound revealed a mass posterior to the left inferior thyroid. A Sestamibi parathyroid scan revealed a parathyroid adenoma at the posteroinferior aspect of the left hemithyroid. Labs for free metanephrines and normetanephrine, prolactin and gastrin levels were all normal. Due to his young age and the possibility of having familial hyperparathyroidism, he underwent bilateral neck exploration and parathyroidectomy, with removal of his left inferior, right superior, left superior parathyroid glands and left upper thymus. Surgical pathology revealed, hypercellular parathyroid tissue. Post operatively, his calcium and vitamin D remained within the normal range. Genetic studies revealed a mutation in the parafibromin gene - CDC73 (also called HRPT2), a tumor suppressor gene, which is on chromosome 1q25. The patient currently has 6 children ranging from age 5 months to 6 years. He was advised to have his children tested any time from age 7 years for the gene mutation. The patient has remained stable 4yrs post operatively, with normal calcium and PTH levels. He does not have any history of jaw tumor. He never had an ultrasound kidney done. He is being monitored with yearly lab tests. Conclusion: CDC73 gene mutation-associated disorders are inherited as an autosomal dominant fashion, with variable penetrance. This gene mutation can be found in conditions such as hyperparathyroidism jaw tumor, familial hyperparathyroidism and parathyroid cancer. Reference: 1. CDC73-Related Disorders: Clinical Manifestations and Case Detection in Primary Hyperparathyroidism. J Clin Endocrinol Metab. 2017 Dec 1;102(12):4534–4540.

scholarly journals A Case Report of Calcium-Sensing Receptor Gene Variant and Primary Hyperparathyroidism

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A173-A174
Author(s):  
Sabaa Salim Joad ◽  
Mary Emily Fang ◽  
Jennifer E Posey ◽  
Ruchi Gaba
Keyword(s):  
Family History ◽  
Receptor Gene ◽  
Pathogenic Variant ◽  
Gene Variant ◽  
Calcium Sensing Receptor ◽  
Subtotal Parathyroidectomy ◽  
Calcium Sensing ◽  
Post Surgery ◽  
History Of ◽  
Calcium Sensing Receptor Gene

Abstract Introduction: Primary hyperparathyroidism (PHPT) is an endocrinopathy that results from excessive production of parathyroid hormone from one or more overactive parathyroid gland(s). An estimated 90% of PHPT cases are sporadic, and 10% are inherited, comprising familial hyperparathyroidism (FHP). In FHP syndromes, variable clinical features are partly attributed to genetic heterogeneity. While there is not a consensus whether Familial hypocalciuric hypercalcemia (FHH) is a distinct entity or a form of FHP, accurate diagnosis is critical in guiding proper decision-making. The utility of genetic testing is multi-fold: help inform most likely diagnosis, guide prognosis and management, and inform familial recurrence risk. We report a patient with early-onset hypercalcemia, post subtotal parathyroidectomy, notable family history, with a likely pathogenic variant in the calcium-sensing receptor gene, CASR. Case Presentation: A 42 yo, female with history of nephrolithiasis and hypercalcemia diagnosed in her 20’s with PHPT was referred to our endocrinology clinic. Preoperative work up showed calcium of 11.1mg/dL, albumin 4.2g/dL, PTH of 177pg/mL, creatinine 0.92mg/dL. Sestamibi showed persistent activity in the mid to inferior aspect of right thyroid lobe suspicious for parathyroid adenoma. She underwent 3 gland parathyroidectomy and pathology showed mildly hypercellular parathyroid in left superior & right superior gland, normocellular left inferior gland. PTH levels normalized post-surgery. PTH levels normalized post surgery. Genetic evaluation was done, given her early-onset hypercalcemia, multi-gland involvement, and notable family history (maternal grandfather with parathyroidectomy for hypercalcemia and mother reportedly undergoing a hyperparathyroidism workup). Invitae hyperparathyroidism genetic panel revealed a likely pathogenic variant in CASR (c.659G&gt;A; p.R220Q). Discussion: To date, our case with PHPT is the second report of the likely pathogenic variant CASR (c.659G&gt;A; p.R220Q), which affects a conserved extracellular domain residue, thought to be important in sensing extracellular calcium. This variant has been previously reported in another family with FHH with 5 affected relatives. The reported 29-year old proband also had recurrent pancreatitis, which resolved with subtotal parathyroidectomy, but remained hypercalcemic. Despite the marked phenotypic heterogeneity in our patient and the case with FHH in terms of clinical presentation and response to treatment with surgery; both shared a history of hyperparathyroidism and a family history of hypercalcemia, suggesting contributions from the same CASR gene variant. With limited existing data about the variable expressivity of variants in genes implicated in the pathogenesis of both FHH and FHP; our case adds value to the existing evidence that supports its possible genetic contribution to PHPT

scholarly journals Atypical Presentation of Familial Hypocalciuric Hypercalcemia: Case Report

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A182-A183
Author(s):  
Dalal S Ali ◽  
Karel Dandurand ◽  
Aliya Aziz Khan
Keyword(s):  
Vitamin D ◽  
Primary Hyperparathyroidism ◽  
Dna Analysis ◽  
Receptor Gene ◽  
Familial Hypocalciuric Hypercalcemia ◽  
Calcium Sensing Receptor ◽  
Clearance Ratio ◽  
Subtotal Parathyroidectomy ◽  
Casr Gene ◽  
Calcium Sensing

Abstract Background: Differentiation between familial hypocalciuric hypercalcemia (FHH) and primary hyperparathyroidism (PHPT) can be challenging in certain cases in the absence of DNA analysis of the calcium sensing receptor gene. The distinction between those two clinical entities with overlapping biochemical features therefore relies on the calcium to creatinine clearance ratio (CCCR), which is expected to be low in FHH (&lt;0.01 in 80% of cases and between 0.01 and 0.02 in approximately 20% of patients)1. Patients with PHPT usually have a CCCR of&gt;= 0.02. A lower CCCR between 0.01 and 0.02 can be seen in approximately 20% of patients1,2and is more commonly seen in the presence of vitamin D insufficiency, impaired renal function, low calcium intake or being of African descent. It is advised to stop drugs which can contribute to hypercalcemia and lower the CCCR such as thiazide diuretics prior to evaluating the CCCR. Clinical Case: A 56-year-old lady was referred for evaluation of persistent hypercalcemia post parathyroidectomy and fatigue. She had mildly elevated ionized serum calcium (iCa) and a mid-normal PTH with a CCCR of 0.024. She had a normal BMD with no prior fragility fractures and passed a kidney stone prior to her presentation. Physical exam was unremarkable. She had previously travelled to Tampa and had a subtotal parathyroidectomy 3 glands (RU, LU, RL) for a possible diagnosis of PHPT, tissue biopsy showed hyperplastic parathyroids. Her MEN1 gene analysis was negative for MEN1 mutation and MRI of the abdomen was unremarkable. Her mother had a diagnosis of PHPT and osteoporosis. The iCa remained mildly elevated at 1.43 mmol/L (1.15–1.3) with a 24 hr urinary CCCR at 0.024 and a mid-normal PTH of 4.4 pmol/L (1.6–6.9). Her eGFR was 104 mls/min, 25 vitamin D 82 nmol/L (75–250), 1,25 dihydroxy vitamin D 122 pmol/L (60–206), PO4 0.90 mmol/L (0.8–1.45) and alkaline phosphatase 46 U/L (35–120) were all normal. She continued to have mild symptoms of hypercalcemia and her bone scan was negative for underlying skeletal pathology. DNA studies for mutations in the CaSR gene were completed. This confirmed the presence of a heterozygous loss of function mutation in the CASR gene at c493-2A&gt;G which appears to be pathogenic. Conclusion: The CCCR is useful in differentiating PHPT from FHH however in certain cases of FHH the CCCR may be higher then expected and we have now confirmed the presence of FHH with a molecular diagnosis in a patient with a CCCR as high as 0.02. References: 1 Gunn, IR, Gaffney, D. Clinical and laboratory features of calcium-sensing receptor disorders: a systematic review. Ann Clin Biochem 2004; 41:441–58 2 Stephen J. Marx, Letter to the Editor: Distinguishing Typical Primary Hyperparathyroidism From Familial Hypocalciuric Hypercalcemia by Using an Index of Urinary Calcium, The Journal of Clinical Endocrinology & Metabolism, 2015

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

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A1001-A1002
Author(s):  
Lisette Patricia Rodriguez ◽  
Jesus B Perez ◽  
Wilhelmine Wiese-Rometsch
Keyword(s):  
Thyroid Cancer ◽  
Lymph Node ◽  
Family History ◽  
Primary Hyperparathyroidism ◽  
Serum Calcitonin ◽  
Medullary Thyroid ◽  
Bilateral Pheochromocytoma ◽  
Patient Reported ◽  
History Of ◽  
Men 2A

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 &lt;= 5) and 276.2 ng/mL (n &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 &lt;= 49-290) ug/24h, plasma metanephrines, including fractionated metanephrine (MN) at 163 (n &lt;= 57) pg/ml, fractionated nor-metanephrine (NMN) at 182 (n &lt;= 148) pg/ml, and total, Free (MN+NMN) metanephrines at 345 (n &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 &lt;= 2 pg/ml, CEA 26.8 ng/mL, MN &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&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.

scholarly journals Prevalence of Pathogenic Germline DICER1 Variants in Young Individuals Thyroidectomised Due to Goitre – A National Danish Cohort

2021 ◽  
Vol 12 ◽  
Author(s):  
Mays Altaraihi ◽  
Thomas van Overeem Hansen ◽  
Eric Santoni-Rugiu ◽  
Maria Rossing ◽  
Åse Krogh Rasmussen ◽  
...  
Keyword(s):  
Family History ◽  
Genetic Counselling ◽  
Multinodular Goitre ◽  
Nodular Goitre ◽  
Gene Testing ◽  
History Of ◽  
Age Limit ◽  
Dicer1 Syndrome ◽  
Time Of Operation ◽  
Common Manifestation

IntroductionDICER1 syndrome encompasses a variety of benign and malignant manifestations including multinodular goitre, which is the most common manifestation among individuals carrying pathogenic DICER1 variants. This is the first study estimating the prevalence of pathogenic DICER1 variants in young individuals with multinodular goitre.MethodsDanish individuals diagnosed with nodular goitre based on thyroidectomy samples in 2001-2016 with the age limit at time of operation being ≤ 25 years were offered germline DICER1 gene testing.ResultsSix of 46 individuals, 13% (CI [3.3;22.7], p &lt;0.05), diagnosed with nodular goitre on the basis of thyroidectomy samples under the age of 25 years had pathogenic germline variants in DICER1. They were found in different pathoanatomical nodular goitre cohorts i.e. nodular goitre (n=2), colloid nodular goitre (n=3) and hyperplastic nodular goitre (n=1).ConclusionsWe recommend referral of patients thyroidectomised due to goitre aged &lt;21 years and patients thyroidectomised due to goitre aged &lt;25 years with a family history of goitre to genetic counselling. Patients of all ages thyroidectomised due to goitre, who are affected by another DICER1 manifestation should be referred to genetic counselling.

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