SAT-LB302 From Urolithiasis to Genetic Testing: An Unusual Presentation of MEN-4 Syndrome
Background:Germline mutations in the CDKN1B gene are responsible for Multiple Endocrine Neoplasia Type 4 (MEN 4) syndrome (Alrezk et al. 2017). Around 20 cases have been reported to date. Here, we report on a new MEN4 family which possibly extends the phenotypic spectrum attributable to germline mut...
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| creator | Alamri, Bader Nasser Palma, Laura Andonian, Sero Foulkes, William D Rivera, Juan Andres |
| description | Background:Germline mutations in the CDKN1B gene are responsible for Multiple Endocrine Neoplasia Type 4 (MEN 4) syndrome (Alrezk et al. 2017). Around 20 cases have been reported to date. Here, we report on a new MEN4 family which possibly extends the phenotypic spectrum attributable to germline mutations in CDKN1B.
Clinical Case: A 56-year-old female presented with urolithiasis & was found to have hypercalcemia (serum calcium of 2.76 mmol/l ref. 2.12-2.62 mmol/l). Workup was in keeping with primary hyperparathyroidism (PHPT) (PTH 28.7 pmol/l ref. 1.50-9.30 pmol/l; phosphorus 0.89 mmol/l ref. 0.80-1.45 mmol/l). Sestamibi & US of the neck revealed no clear parathyroid adenoma. Two incidental thyroid nodules were benign on FNA cytology.
The patient underwent neck exploration & a single enlarged parathyroid gland was removed. Pathology showed an enlarged hypercellular gland. Her calcium & PTH normalized after surgery but recurrence was documented a year later. Her family history was significant for PHPT in two brothers & a history of kidney stones in a third brother. Multi-gene panel testing (CASR, CDC73, CDKN1B, MEN1, RET, Invitae Corp.) revealed a pathogenic variant (PV) in CDKN1B (c.215delG). The patient underwent a 2 ½ parathyroidectomy with subsequent normalization of her calcium & PTH. Further work-up showed a 4.5mm non-secreting pituitary adenoma. Plasma metanephrines & NE were intermittently elevated. Serum gastrin was also mildly elevated 83 pmol/l ( |
| doi_str_mv | 10.1210/jendso/bvaa046.2080 |
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| fullrecord | <record><control><sourceid>pubmedcentral_cross</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7208855</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>pubmedcentral_primary_oai_pubmedcentral_nih_gov_7208855</sourcerecordid><originalsourceid>FETCH-LOGICAL-c1440-91716cfd46f4a889d5e7540c75badba1abb006371d7dd6a42fa6b98d86703a643</originalsourceid><addsrcrecordid>eNpVkF1rwjAUhsPYYOL8BbvJH6gmbZq0uxg4UTdwH6Be7CqcNqlGaiJJFfz3q1TGdnVeOLwPLw9Cj5QMaUzJaKetCm5UnAAI48OYZOQG9WIm4ojmIr79k-_RIIQdIYTmCcsZ66Hv5XgVLV4SEuOZd3u89q42zdZAMAE3Ds-11Y0p8UqHxtjNEx5bvLbHcIQaf3kdtG2gMc5iV-H36UfE8PJsVUvSD-iugjrowfX20Xo2XU1eo8Xn_G0yXkQlZYxEORWUl5VivGKQZblKtUgZKUVagCqAQlEQwhNBlVCKA4sr4EWeqYwLkgBnSR89d9zDsdhrVbaLPNTy4M0e_Fk6MPL_x5qt3LiTFK2pLE1bQNIBSu9C8Lr67VIiL4ZlZ1heDcuL4eQH531yIw</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>SAT-LB302 From Urolithiasis to Genetic Testing: An Unusual Presentation of MEN-4 Syndrome</title><source>DOAJ Directory of Open Access Journals</source><source>Oxford Journals Open Access Collection</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><creator>Alamri, Bader Nasser ; Palma, Laura ; Andonian, Sero ; Foulkes, William D ; Rivera, Juan Andres</creator><creatorcontrib>Alamri, Bader Nasser ; Palma, Laura ; Andonian, Sero ; Foulkes, William D ; Rivera, Juan Andres</creatorcontrib><description><![CDATA[Background:Germline mutations in the CDKN1B gene are responsible for Multiple Endocrine Neoplasia Type 4 (MEN 4) syndrome (Alrezk et al. 2017). Around 20 cases have been reported to date. Here, we report on a new MEN4 family which possibly extends the phenotypic spectrum attributable to germline mutations in CDKN1B.
Clinical Case: A 56-year-old female presented with urolithiasis & was found to have hypercalcemia (serum calcium of 2.76 mmol/l ref. 2.12-2.62 mmol/l). Workup was in keeping with primary hyperparathyroidism (PHPT) (PTH 28.7 pmol/l ref. 1.50-9.30 pmol/l; phosphorus 0.89 mmol/l ref. 0.80-1.45 mmol/l). Sestamibi & US of the neck revealed no clear parathyroid adenoma. Two incidental thyroid nodules were benign on FNA cytology.
The patient underwent neck exploration & a single enlarged parathyroid gland was removed. Pathology showed an enlarged hypercellular gland. Her calcium & PTH normalized after surgery but recurrence was documented a year later. Her family history was significant for PHPT in two brothers & a history of kidney stones in a third brother. Multi-gene panel testing (CASR, CDC73, CDKN1B, MEN1, RET, Invitae Corp.) revealed a pathogenic variant (PV) in CDKN1B (c.215delG). The patient underwent a 2 ½ parathyroidectomy with subsequent normalization of her calcium & PTH. Further work-up showed a 4.5mm non-secreting pituitary adenoma. Plasma metanephrines & NE were intermittently elevated. Serum gastrin was also mildly elevated 83 pmol/l (<53 pmol/l). A Ga68-DOTATATE PET scan was negative. Her 23-year-old daughter tested positive for the familial PV. She is asymptomatic & has normal calcium & PTH; pituitary function is normal except for an elevated IGF-1 at 63.9 nmol/l (ref 13.3- 42.6 nmol/l) with borderline growth hormone during OGTT (0.40 ug/l). Her pituitary MRI was normal. One brother with history of prostate cancer, PHPT & partial parathyroidectomy has tested positive for the familial CDKN1B variant. A second brother was also found to carry the familial variant & was clinically asymptomatic.Endocrinological workup has revealed he has PHPT, elevated chromogranin A at 196.2 ng/ml (ref <=82), calcitonin at 25 ng/l (normal <=9 ng/l), IFG1 (35.3 nmol/L ref. 13-21) but normal plasma metanephrines. An MRI of the sella shows an 8mm hypoenhancing lesion. On CT, a retroperitoneal hyperenhancing 4cm mass adjacent to the left ilio-psoas was seen, in keeping with a paraganglioma; additionally, he has a congenital left atrophic kidney & ureter. Two additional brothers; one with history of non-Hodgkin’s lymphoma, PHPT & partial parathyroidectomy & a second brother, also with prostate cancer & recurrent renal stones, have yet to be tested.
Conclusions: A new MEN4 family is described here which expands the spectrum of clinical manifestations of this syndrome. Of great interest in our cases is the presence of paraganglioma, urological malformation, & pre-clinical GH/IGF1 elevation.]]></description><identifier>ISSN: 2472-1972</identifier><identifier>EISSN: 2472-1972</identifier><identifier>DOI: 10.1210/jendso/bvaa046.2080</identifier><language>eng</language><publisher>US: Oxford University Press</publisher><subject>Tumor Biology</subject><ispartof>Journal of the Endocrine Society, 2020-05, Vol.4 (Supplement_1)</ispartof><rights>Endocrine Society 2020. 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7208855/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7208855/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,724,777,781,861,882,27906,27907,53773,53775</link.rule.ids></links><search><creatorcontrib>Alamri, Bader Nasser</creatorcontrib><creatorcontrib>Palma, Laura</creatorcontrib><creatorcontrib>Andonian, Sero</creatorcontrib><creatorcontrib>Foulkes, William D</creatorcontrib><creatorcontrib>Rivera, Juan Andres</creatorcontrib><title>SAT-LB302 From Urolithiasis to Genetic Testing: An Unusual Presentation of MEN-4 Syndrome</title><title>Journal of the Endocrine Society</title><description><![CDATA[Background:Germline mutations in the CDKN1B gene are responsible for Multiple Endocrine Neoplasia Type 4 (MEN 4) syndrome (Alrezk et al. 2017). Around 20 cases have been reported to date. Here, we report on a new MEN4 family which possibly extends the phenotypic spectrum attributable to germline mutations in CDKN1B.
Clinical Case: A 56-year-old female presented with urolithiasis & was found to have hypercalcemia (serum calcium of 2.76 mmol/l ref. 2.12-2.62 mmol/l). Workup was in keeping with primary hyperparathyroidism (PHPT) (PTH 28.7 pmol/l ref. 1.50-9.30 pmol/l; phosphorus 0.89 mmol/l ref. 0.80-1.45 mmol/l). Sestamibi & US of the neck revealed no clear parathyroid adenoma. Two incidental thyroid nodules were benign on FNA cytology.
The patient underwent neck exploration & a single enlarged parathyroid gland was removed. Pathology showed an enlarged hypercellular gland. Her calcium & PTH normalized after surgery but recurrence was documented a year later. Her family history was significant for PHPT in two brothers & a history of kidney stones in a third brother. Multi-gene panel testing (CASR, CDC73, CDKN1B, MEN1, RET, Invitae Corp.) revealed a pathogenic variant (PV) in CDKN1B (c.215delG). The patient underwent a 2 ½ parathyroidectomy with subsequent normalization of her calcium & PTH. Further work-up showed a 4.5mm non-secreting pituitary adenoma. Plasma metanephrines & NE were intermittently elevated. Serum gastrin was also mildly elevated 83 pmol/l (<53 pmol/l). A Ga68-DOTATATE PET scan was negative. Her 23-year-old daughter tested positive for the familial PV. She is asymptomatic & has normal calcium & PTH; pituitary function is normal except for an elevated IGF-1 at 63.9 nmol/l (ref 13.3- 42.6 nmol/l) with borderline growth hormone during OGTT (0.40 ug/l). Her pituitary MRI was normal. One brother with history of prostate cancer, PHPT & partial parathyroidectomy has tested positive for the familial CDKN1B variant. A second brother was also found to carry the familial variant & was clinically asymptomatic.Endocrinological workup has revealed he has PHPT, elevated chromogranin A at 196.2 ng/ml (ref <=82), calcitonin at 25 ng/l (normal <=9 ng/l), IFG1 (35.3 nmol/L ref. 13-21) but normal plasma metanephrines. An MRI of the sella shows an 8mm hypoenhancing lesion. On CT, a retroperitoneal hyperenhancing 4cm mass adjacent to the left ilio-psoas was seen, in keeping with a paraganglioma; additionally, he has a congenital left atrophic kidney & ureter. Two additional brothers; one with history of non-Hodgkin’s lymphoma, PHPT & partial parathyroidectomy & a second brother, also with prostate cancer & recurrent renal stones, have yet to be tested.
Conclusions: A new MEN4 family is described here which expands the spectrum of clinical manifestations of this syndrome. Of great interest in our cases is the presence of paraganglioma, urological malformation, & pre-clinical GH/IGF1 elevation.]]></description><subject>Tumor Biology</subject><issn>2472-1972</issn><issn>2472-1972</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNpVkF1rwjAUhsPYYOL8BbvJH6gmbZq0uxg4UTdwH6Be7CqcNqlGaiJJFfz3q1TGdnVeOLwPLw9Cj5QMaUzJaKetCm5UnAAI48OYZOQG9WIm4ojmIr79k-_RIIQdIYTmCcsZ66Hv5XgVLV4SEuOZd3u89q42zdZAMAE3Ds-11Y0p8UqHxtjNEx5bvLbHcIQaf3kdtG2gMc5iV-H36UfE8PJsVUvSD-iugjrowfX20Xo2XU1eo8Xn_G0yXkQlZYxEORWUl5VivGKQZblKtUgZKUVagCqAQlEQwhNBlVCKA4sr4EWeqYwLkgBnSR89d9zDsdhrVbaLPNTy4M0e_Fk6MPL_x5qt3LiTFK2pLE1bQNIBSu9C8Lr67VIiL4ZlZ1heDcuL4eQH531yIw</recordid><startdate>20200508</startdate><enddate>20200508</enddate><creator>Alamri, Bader Nasser</creator><creator>Palma, Laura</creator><creator>Andonian, Sero</creator><creator>Foulkes, William D</creator><creator>Rivera, Juan Andres</creator><general>Oxford University Press</general><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope></search><sort><creationdate>20200508</creationdate><title>SAT-LB302 From Urolithiasis to Genetic Testing: An Unusual Presentation of MEN-4 Syndrome</title><author>Alamri, Bader Nasser ; Palma, Laura ; Andonian, Sero ; Foulkes, William D ; Rivera, Juan Andres</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c1440-91716cfd46f4a889d5e7540c75badba1abb006371d7dd6a42fa6b98d86703a643</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Tumor Biology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Alamri, Bader Nasser</creatorcontrib><creatorcontrib>Palma, Laura</creatorcontrib><creatorcontrib>Andonian, Sero</creatorcontrib><creatorcontrib>Foulkes, William D</creatorcontrib><creatorcontrib>Rivera, Juan Andres</creatorcontrib><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of the Endocrine Society</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Alamri, Bader Nasser</au><au>Palma, Laura</au><au>Andonian, Sero</au><au>Foulkes, William D</au><au>Rivera, Juan Andres</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>SAT-LB302 From Urolithiasis to Genetic Testing: An Unusual Presentation of MEN-4 Syndrome</atitle><jtitle>Journal of the Endocrine Society</jtitle><date>2020-05-08</date><risdate>2020</risdate><volume>4</volume><issue>Supplement_1</issue><issn>2472-1972</issn><eissn>2472-1972</eissn><abstract><![CDATA[Background:Germline mutations in the CDKN1B gene are responsible for Multiple Endocrine Neoplasia Type 4 (MEN 4) syndrome (Alrezk et al. 2017). Around 20 cases have been reported to date. Here, we report on a new MEN4 family which possibly extends the phenotypic spectrum attributable to germline mutations in CDKN1B.
Clinical Case: A 56-year-old female presented with urolithiasis & was found to have hypercalcemia (serum calcium of 2.76 mmol/l ref. 2.12-2.62 mmol/l). Workup was in keeping with primary hyperparathyroidism (PHPT) (PTH 28.7 pmol/l ref. 1.50-9.30 pmol/l; phosphorus 0.89 mmol/l ref. 0.80-1.45 mmol/l). Sestamibi & US of the neck revealed no clear parathyroid adenoma. Two incidental thyroid nodules were benign on FNA cytology.
The patient underwent neck exploration & a single enlarged parathyroid gland was removed. Pathology showed an enlarged hypercellular gland. Her calcium & PTH normalized after surgery but recurrence was documented a year later. Her family history was significant for PHPT in two brothers & a history of kidney stones in a third brother. Multi-gene panel testing (CASR, CDC73, CDKN1B, MEN1, RET, Invitae Corp.) revealed a pathogenic variant (PV) in CDKN1B (c.215delG). The patient underwent a 2 ½ parathyroidectomy with subsequent normalization of her calcium & PTH. Further work-up showed a 4.5mm non-secreting pituitary adenoma. Plasma metanephrines & NE were intermittently elevated. Serum gastrin was also mildly elevated 83 pmol/l (<53 pmol/l). A Ga68-DOTATATE PET scan was negative. Her 23-year-old daughter tested positive for the familial PV. She is asymptomatic & has normal calcium & PTH; pituitary function is normal except for an elevated IGF-1 at 63.9 nmol/l (ref 13.3- 42.6 nmol/l) with borderline growth hormone during OGTT (0.40 ug/l). Her pituitary MRI was normal. One brother with history of prostate cancer, PHPT & partial parathyroidectomy has tested positive for the familial CDKN1B variant. A second brother was also found to carry the familial variant & was clinically asymptomatic.Endocrinological workup has revealed he has PHPT, elevated chromogranin A at 196.2 ng/ml (ref <=82), calcitonin at 25 ng/l (normal <=9 ng/l), IFG1 (35.3 nmol/L ref. 13-21) but normal plasma metanephrines. An MRI of the sella shows an 8mm hypoenhancing lesion. On CT, a retroperitoneal hyperenhancing 4cm mass adjacent to the left ilio-psoas was seen, in keeping with a paraganglioma; additionally, he has a congenital left atrophic kidney & ureter. Two additional brothers; one with history of non-Hodgkin’s lymphoma, PHPT & partial parathyroidectomy & a second brother, also with prostate cancer & recurrent renal stones, have yet to be tested.
Conclusions: A new MEN4 family is described here which expands the spectrum of clinical manifestations of this syndrome. Of great interest in our cases is the presence of paraganglioma, urological malformation, & pre-clinical GH/IGF1 elevation.]]></abstract><cop>US</cop><pub>Oxford University Press</pub><doi>10.1210/jendso/bvaa046.2080</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Tumor Biology |
| title | SAT-LB302 From Urolithiasis to Genetic Testing: An Unusual Presentation of MEN-4 Syndrome |
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