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Paragangliomas 4(PGL4)

MedGen UID:
349380
Concept ID:
C1861848
Neoplastic Process
Synonyms: CAROTID BODY TUMORS AND MULTIPLE EXTRAADRENAL PHEOCHROMOCYTOMAS; Paraganglioma, familial malignant; Paragangliomas, hereditary extraadrenal; PGL4; Pheochromocytoma, extraadrenal and cervical paraganglioma; Pheochromocytoma, familial extraadrenal; SDHB-Related Hereditary Paraganglioma-Pheochromocytoma Syndrome; SDHB-Related Hereditary Paraganglioma-Pheochromocytoma Syndrome (Paragangliomas 4)
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Sources: HPO, OMIM
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Gene (location): SDHB (1p36.13)
 
Monarch Initiative: MONDO:0007273
OMIM®: 115310

Disease characteristics

Hereditary paraganglioma-pheochromocytoma (PGL/PCC) syndromes are characterized by paragangliomas (tumors that arise from neuroendocrine tissues distributed along the paravertebral axis from the base of the skull to the pelvis) and pheochromocytomas (paragangliomas that are confined to the adrenal medulla). Sympathetic paragangliomas cause catecholamine excess; parasympathetic paragangliomas are most often nonsecretory. Extra-adrenal parasympathetic paragangliomas are located predominantly in the skull base and neck (referred to as head and neck PGL [HNPGL]) and sometimes in the upper mediastinum; approximately 95% of such tumors are nonsecretory. In contrast, sympathetic extra-adrenal paragangliomas are generally confined to the lower mediastinum, abdomen, and pelvis, and are typically secretory. Pheochromocytomas, which arise from the adrenal medulla, typically lead to catecholamine excess. Symptoms of PGL/PCC result from either mass effects or catecholamine hypersecretion (e.g., sustained or paroxysmal elevations in blood pressure, headache, episodic profuse sweating, forceful palpitations, pallor, and apprehension or anxiety). The risk for developing metastatic disease is greater for extra-adrenal sympathetic paragangliomas than for pheochromocytomas. [from GeneReviews]
Authors:
Tobi Else  |  Samantha Greenberg  |  Lauren Fishbein   view full author information

Additional descriptions

From MedlinePlus Genetics
Paragangliomas and pheochromocytomas can occur in individuals with other inherited disorders, such as von Hippel-Lindau syndrome, Carney-Stratakis syndrome, and certain types of multiple endocrine neoplasia. These other disorders feature additional tumor types and have different genetic causes. Some paragangliomas and pheochromocytomas occur in people with no history of the tumors in their families and appear not to be inherited. These cases are designated as sporadic.\n\nResearchers have identified several types of hereditary paraganglioma-pheochromocytoma. Each type is distinguished by its genetic cause. People with types 1, 2, and 3 typically develop paragangliomas in the head or neck region. People with type 4 usually develop extra-adrenal paragangliomas in the abdomen and are at higher risk for malignant tumors that metastasize. The other types are very rare. Hereditary paraganglioma-pheochromocytoma is typically diagnosed in a person's 30s.\n\nAlthough most paragangliomas and pheochromocytomas are noncancerous, some can become cancerous (malignant) and spread to other parts of the body (metastasize). Extra-adrenal paragangliomas become malignant more often than other types of paraganglioma or pheochromocytoma.\n\nMost paragangliomas are associated with ganglia of the parasympathetic nervous system, which controls involuntary body functions such as digestion and saliva formation. Parasympathetic paragangliomas, typically found in the head and neck, usually do not produce hormones. However, large tumors may cause signs and symptoms such as coughing, hearing loss in one ear, or difficulty swallowing.\n\nPheochromocytomas and some other paragangliomas are associated with ganglia of the sympathetic nervous system. The sympathetic nervous system controls the "fight-or-flight" response, a series of changes in the body due to hormones released in response to stress. Sympathetic paragangliomas found outside the adrenal glands, usually in the abdomen, are called extra-adrenal paragangliomas. Most sympathetic paragangliomas, including pheochromocytomas, produce hormones called catecholamines, such as epinephrine (adrenaline) or norepinephrine. These excess catecholamines can cause signs and symptoms such as high blood pressure (hypertension), episodes of rapid heartbeat (palpitations), headaches, or sweating.\n\nHereditary paraganglioma-pheochromocytoma is an inherited condition characterized by the growth of noncancerous (benign) tumors in structures called paraganglia. Paraganglia are groups of cells that are found near nerve cell bunches called ganglia. A tumor involving the paraganglia is known as a paraganglioma. A type of paraganglioma known as a pheochromocytoma develops in the adrenal glands, which are located on top of each kidney and produce hormones in response to stress. Other types of paraganglioma are usually found in the head, neck, or trunk. People with hereditary paraganglioma-pheochromocytoma develop one or more paragangliomas, which may include pheochromocytomas.  https://medlineplus.gov/genetics/condition/hereditary-paraganglioma-pheochromocytoma
From MedlinePlus Genetics
Researchers have identified several types of hereditary paraganglioma-pheochromocytoma. Each type is distinguished by its genetic cause. People with types 1, 2, and 3 typically develop paragangliomas in the head or neck region. People with type 4 usually develop extra-adrenal paragangliomas in the abdomen and are at higher risk for malignant tumors that metastasize. The other types are very rare. Hereditary paraganglioma-pheochromocytoma is typically diagnosed in a person's 30s.\n\nParagangliomas and pheochromocytomas can occur in individuals with other inherited disorders, such as von Hippel-Lindau syndrome, Carney-Stratakis syndrome, and certain types of multiple endocrine neoplasia. These other disorders feature additional tumor types and have different genetic causes. Some paragangliomas and pheochromocytomas occur in people with no history of the tumors in their families and appear not to be inherited. These cases are designated as sporadic.\n\nAlthough most paragangliomas and pheochromocytomas are noncancerous, some can become cancerous (malignant) and spread to other parts of the body (metastasize). Extra-adrenal paragangliomas become malignant more often than other types of paraganglioma or pheochromocytoma.\n\nMost paragangliomas are associated with ganglia of the parasympathetic nervous system, which controls involuntary body functions such as digestion and saliva formation. Parasympathetic paragangliomas, typically found in the head and neck, usually do not produce hormones. However, large tumors may cause signs and symptoms such as coughing, hearing loss in one ear, or difficulty swallowing.\n\nPheochromocytomas and some other paragangliomas are associated with ganglia of the sympathetic nervous system. The sympathetic nervous system controls the "fight-or-flight" response, a series of changes in the body due to hormones released in response to stress. Sympathetic paragangliomas found outside the adrenal glands, usually in the abdomen, are called extra-adrenal paragangliomas. Most sympathetic paragangliomas, including pheochromocytomas, produce hormones called catecholamines, such as epinephrine (adrenaline) or norepinephrine. These excess catecholamines can cause signs and symptoms such as high blood pressure (hypertension), episodes of rapid heartbeat (palpitations), headaches, or sweating.\n\nHereditary paraganglioma-pheochromocytoma is an inherited condition characterized by the growth of noncancerous (benign) tumors in structures called paraganglia. Paraganglia are groups of cells that are found near nerve cell bunches called ganglia. A tumor involving the paraganglia is known as a paraganglioma. A type of paraganglioma known as a pheochromocytoma develops in the adrenal glands, which are located on top of each kidney and produce hormones in response to stress. Other types of paraganglioma are usually found in the head, neck, or trunk. People with hereditary paraganglioma-pheochromocytoma develop one or more paragangliomas, which may include pheochromocytomas.  https://medlineplus.gov/genetics/condition/hereditary-paraganglioma-pheochromocytoma

Clinical features

From HPO
Renal cell carcinoma
MedGen UID:
766
Concept ID:
C0007134
Neoplastic Process
A carcinoma arising from the renal parenchyma. There is a strong correlation between cigarette smoking and the development of renal cell carcinoma. The clinical presentation includes : hematuria, flank pain and a palpable lumbar mass. A high percentage of renal cell carcinomas are diagnosed when an ultrasound is performed for other purposes. Radical nephrectomy is the standard intervention procedure. Renal cell carcinoma is generally considered to be resistant to radiation treatment and chemotherapy.
Carotid body paraganglioma
MedGen UID:
2853
Concept ID:
C0007279
Neoplastic Process
A usually benign neoplasm originating in the chemoreceptor tissue of the carotid body, glomus jugulare, glomus tympanicum, aortic bodies, or the female genital tract.
Glomus jugular tumor
MedGen UID:
4905
Concept ID:
C0017671
Neoplastic Process
A benign or malignant extra-adrenal parasympathetic paraganglioma arising from paraganglia in the base of the skull and middle ear.
Neoplasm
MedGen UID:
10294
Concept ID:
C0027651
Neoplastic Process
A benign or malignant tissue growth resulting from uncontrolled cell proliferation. Benign neoplastic cells resemble normal cells without exhibiting significant cytologic atypia, while malignant cells exhibit overt signs such as dysplastic features, atypical mitotic figures, necrosis, nuclear pleomorphism, and anaplasia. Representative examples of benign neoplasms include papillomas, cystadenomas, and lipomas; malignant neoplasms include carcinomas, sarcomas, lymphomas, and leukemias.
Neuroblastoma
MedGen UID:
18012
Concept ID:
C0027819
Neoplastic Process
ALK-related neuroblastic tumor susceptibility is characterized by increased risk for neuroblastic tumors including neuroblastoma, ganglioneuroblastoma, and ganglioneuroma. Neuroblastoma is a more malignant tumor and ganglioneuroma a more benign tumor. Depending on the histologic findings, ganglioneuroblastoma can behave in a more aggressive fashion, like neuroblastoma, or in a benign fashion, like ganglioneuroma. Preliminary data from the ten reported families with ALK-related neuroblastic tumor susceptibility suggest an overall penetrance of approximately 57% with the risk for neuroblastic tumor development highest in infancy and decreasing by late childhood.
Paraganglioma
MedGen UID:
10571
Concept ID:
C0030421
Neoplastic Process
A carotid body tumor (also called paraganglionoma or chemodectoma) is a tumor found in the upper neck at the branching of the carotid artery. They arise from the chemoreceptor organ (paraganglion) located in the adventitia of the carotid artery bifurcation.
Gastrointestinal stroma tumor
MedGen UID:
116049
Concept ID:
C0238198
Neoplastic Process
Gastrointestinal stromal tumors are mesenchymal tumors found in the gastrointestinal tract that originate from the interstitial cells of Cajal, the pacemaker cells that regulate peristalsis in the digestive tract. Approximately 70% of GISTs develop in the stomach, 20% in the small intestine, and less than 10% in the esophagus, colon, and rectum. GISTs are typically more cellular than other gastrointestinal sarcomas. They occur predominantly in patients who are 40 to 70 years old but in rare cases may occur in younger persons (Miettinen et al., 1999, 1999). GISTs are also seen as a feature in several syndromes, e.g., neurofibromatosis-1 (NF1; 162200) and GIST-plus syndrome (175510).
Extraadrenal pheochromocytoma
MedGen UID:
263453
Concept ID:
C1257877
Neoplastic Process
Pheochromocytoma not originating from the adrenal medulla but from another source such as from chromaffin cells in or about sympathetic ganglia.
Paraganglioma of head and neck
MedGen UID:
232588
Concept ID:
C1333944
Neoplastic Process
A benign or malignant extra-adrenal paraganglioma arising from paraganglia in the head and neck. Representative examples include the carotid body and jugulotympanic paragangliomas.
Adrenal pheochromocytoma
MedGen UID:
1636437
Concept ID:
C4551683
Neoplastic Process
Pheochromocytoma originating from the adrenal medulla.
Renal cell carcinoma
MedGen UID:
766
Concept ID:
C0007134
Neoplastic Process
A carcinoma arising from the renal parenchyma. There is a strong correlation between cigarette smoking and the development of renal cell carcinoma. The clinical presentation includes : hematuria, flank pain and a palpable lumbar mass. A high percentage of renal cell carcinomas are diagnosed when an ultrasound is performed for other purposes. Radical nephrectomy is the standard intervention procedure. Renal cell carcinoma is generally considered to be resistant to radiation treatment and chemotherapy.
Elevated urinary catecholamines
MedGen UID:
488807
Concept ID:
C0241577
Finding
An increased concentration of catecholamine in the urine.
Palpitations
MedGen UID:
14579
Concept ID:
C0030252
Finding
A sensation that the heart is pounding or racing, which is a non-specific sign but may be a manifestation of arrhythmia.
Tachycardia
MedGen UID:
21453
Concept ID:
C0039231
Finding
A rapid heartrate that exceeds the range of the normal resting heartrate for age.
Hypertension associated with pheochromocytoma
MedGen UID:
871214
Concept ID:
C4025693
Disease or Syndrome
A type of hypertension associated with pheochromocytoma.
Gastrointestinal stroma tumor
MedGen UID:
116049
Concept ID:
C0238198
Neoplastic Process
Gastrointestinal stromal tumors are mesenchymal tumors found in the gastrointestinal tract that originate from the interstitial cells of Cajal, the pacemaker cells that regulate peristalsis in the digestive tract. Approximately 70% of GISTs develop in the stomach, 20% in the small intestine, and less than 10% in the esophagus, colon, and rectum. GISTs are typically more cellular than other gastrointestinal sarcomas. They occur predominantly in patients who are 40 to 70 years old but in rare cases may occur in younger persons (Miettinen et al., 1999, 1999). GISTs are also seen as a feature in several syndromes, e.g., neurofibromatosis-1 (NF1; 162200) and GIST-plus syndrome (175510).
Pulsatile tinnitus
MedGen UID:
148340
Concept ID:
C0751559
Sign or Symptom
Carotid body paraganglioma
MedGen UID:
2853
Concept ID:
C0007279
Neoplastic Process
A usually benign neoplasm originating in the chemoreceptor tissue of the carotid body, glomus jugulare, glomus tympanicum, aortic bodies, or the female genital tract.
Glomus jugular tumor
MedGen UID:
4905
Concept ID:
C0017671
Neoplastic Process
A benign or malignant extra-adrenal parasympathetic paraganglioma arising from paraganglia in the base of the skull and middle ear.
Neuroblastoma
MedGen UID:
18012
Concept ID:
C0027819
Neoplastic Process
ALK-related neuroblastic tumor susceptibility is characterized by increased risk for neuroblastic tumors including neuroblastoma, ganglioneuroblastoma, and ganglioneuroma. Neuroblastoma is a more malignant tumor and ganglioneuroma a more benign tumor. Depending on the histologic findings, ganglioneuroblastoma can behave in a more aggressive fashion, like neuroblastoma, or in a benign fashion, like ganglioneuroma. Preliminary data from the ten reported families with ALK-related neuroblastic tumor susceptibility suggest an overall penetrance of approximately 57% with the risk for neuroblastic tumor development highest in infancy and decreasing by late childhood.
Paraganglioma
MedGen UID:
10571
Concept ID:
C0030421
Neoplastic Process
A carotid body tumor (also called paraganglionoma or chemodectoma) is a tumor found in the upper neck at the branching of the carotid artery. They arise from the chemoreceptor organ (paraganglion) located in the adventitia of the carotid artery bifurcation.
Cranial nerve paralysis
MedGen UID:
57717
Concept ID:
C0151311
Disease or Syndrome
Injury to any of the cranial nerves or their nuclei in the brain resulting in muscle weakness.
Extraadrenal pheochromocytoma
MedGen UID:
263453
Concept ID:
C1257877
Neoplastic Process
Pheochromocytoma not originating from the adrenal medulla but from another source such as from chromaffin cells in or about sympathetic ganglia.
Paraganglioma of head and neck
MedGen UID:
232588
Concept ID:
C1333944
Neoplastic Process
A benign or malignant extra-adrenal paraganglioma arising from paraganglia in the head and neck. Representative examples include the carotid body and jugulotympanic paragangliomas.
Episodic paroxysmal anxiety
MedGen UID:
923185
Concept ID:
C1387805
Mental or Behavioral Dysfunction
Recurrent attacks of severe anxiety, whose occurence is not restricted to any particular situation or set of circumstances and is therefore unpredictable.
Recurrent paroxysmal headache
MedGen UID:
927617
Concept ID:
C4293708
Sign or Symptom
Repeated episodes of headache with rapid onset, reaching a peak within minutes and of short duration (less than one hour) with pain that is throbbing, pulsating, or bursting in quality.
Adrenal pheochromocytoma
MedGen UID:
1636437
Concept ID:
C4551683
Neoplastic Process
Pheochromocytoma originating from the adrenal medulla.
Elevated urinary catecholamines
MedGen UID:
488807
Concept ID:
C0241577
Finding
An increased concentration of catecholamine in the urine.
Hyperhidrosis
MedGen UID:
5690
Concept ID:
C0020458
Finding
Abnormal excessive perspiration (sweating) despite the lack of appropriate stimuli like hot and humid weather.
Carotid body paraganglioma
MedGen UID:
2853
Concept ID:
C0007279
Neoplastic Process
A usually benign neoplasm originating in the chemoreceptor tissue of the carotid body, glomus jugulare, glomus tympanicum, aortic bodies, or the female genital tract.
Glomus jugular tumor
MedGen UID:
4905
Concept ID:
C0017671
Neoplastic Process
A benign or malignant extra-adrenal parasympathetic paraganglioma arising from paraganglia in the base of the skull and middle ear.
Paraganglioma
MedGen UID:
10571
Concept ID:
C0030421
Neoplastic Process
A carotid body tumor (also called paraganglionoma or chemodectoma) is a tumor found in the upper neck at the branching of the carotid artery. They arise from the chemoreceptor organ (paraganglion) located in the adventitia of the carotid artery bifurcation.
Extraadrenal pheochromocytoma
MedGen UID:
263453
Concept ID:
C1257877
Neoplastic Process
Pheochromocytoma not originating from the adrenal medulla but from another source such as from chromaffin cells in or about sympathetic ganglia.
Paraganglioma of head and neck
MedGen UID:
232588
Concept ID:
C1333944
Neoplastic Process
A benign or malignant extra-adrenal paraganglioma arising from paraganglia in the head and neck. Representative examples include the carotid body and jugulotympanic paragangliomas.
Adrenal pheochromocytoma
MedGen UID:
1636437
Concept ID:
C4551683
Neoplastic Process
Pheochromocytoma originating from the adrenal medulla.

Professional guidelines

PubMed

Hampel H, Bennett RL, Buchanan A, Pearlman R, Wiesner GL; Guideline Development Group, American College of Medical Genetics and Genomics Professional Practice and Guidelines Committee and National Society of Genetic Counselors Practice Guidelines Committee.
Genet Med 2015 Jan;17(1):70-87. Epub 2014 Nov 13 doi: 10.1038/gim.2014.147. PMID: 25394175
ACMG Board of Directors.
Genet Med 2015 Jan;17(1):68-9. Epub 2014 Nov 13 doi: 10.1038/gim.2014.151. PMID: 25356965
Lenders JW, Duh QY, Eisenhofer G, Gimenez-Roqueplo AP, Grebe SK, Murad MH, Naruse M, Pacak K, Young WF Jr; Endocrine Society.
J Clin Endocrinol Metab 2014 Jun;99(6):1915-42. doi: 10.1210/jc.2014-1498. PMID: 24893135
Reaume MN, Graham GE, Tomiak E, Kamel-Reid S, Jewett MA, Bjarnason GA, Blais N, Care M, Drachenberg D, Gedye C, Grant R, Heng DY, Kapoor A, Kollmannsberger C, Lattouf JB, Maher ER, Pause A, Ruether D, Soulieres D, Tanguay S, Turcotte S, Violette PD, Wood L, Basiuk J, Pautler SE; Kidney Cancer Research Network of Canada.
Can Urol Assoc J 2013 Sep-Oct;7(9-10):319-23. doi: 10.5489/cuaj.1496. PMID: 24319509Free PMC Article
Green RC, Berg JS, Grody WW, Kalia SS, Korf BR, Martin CL, McGuire AL, Nussbaum RL, O'Daniel JM, Ormond KE, Rehm HL, Watson MS, Williams MS, Biesecker LG; American College of Medical Genetics and Genomics.
Genet Med 2013 Jul;15(7):565-74. Epub 2013 Jun 20 doi: 10.1038/gim.2013.73. PMID: 23788249Free PMC Article
Chen H, Sippel RS, O'Dorisio MS, Vinik AI, Lloyd RV, Pacak K; North American Neuroendocrine Tumor Society (NANETS).
Pancreas 2010 Aug;39(6):775-83. doi: 10.1097/MPA.0b013e3181ebb4f0. PMID: 20664475Free PMC Article
Robson ME, Storm CD, Weitzel J, Wollins DS, Offit K; American Society of Clinical Oncology.
J Clin Oncol 2010 Feb 10;28(5):893-901. Epub 2010 Jan 11 doi: 10.1200/JCO.2009.27.0660. PMID: 20065170
Zon RT, Goss E, Vogel VG, Chlebowski RT, Jatoi I, Robson ME, Wollins DS, Garber JE, Brown P, Kramer BS; American Society of Clinical Oncology.
J Clin Oncol 2009 Feb 20;27(6):986-93. Epub 2008 Dec 15 doi: 10.1200/JCO.2008.16.3691. PMID: 19075281Free PMC Article

External

Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 update (ACMG SF v2.0): a policy statement of the American College of Medical Genetics and Genomics.

ACMG SF v3.0, 2021

Recent clinical studies

Etiology

Niemeijer ND, Rijken JA, Eijkelenkamp K, van der Horst-Schrivers ANA, Kerstens MN, Tops CMJ, van Berkel A, Timmers HJLM, Kunst HPM, Leemans CR, Bisschop PH, Dreijerink KMA, van Dooren MF, Bayley JP, Pereira AM, Jansen JC, Hes FJ, Hensen EF, Corssmit EPM
Eur J Endocrinol 2017 Aug;177(2):115-125. Epub 2017 May 10 doi: 10.1530/EJE-17-0074. PMID: 28490599
Piazza P, Di Lella F, Bacciu A, Di Trapani G, Ait Mimoune H, Sanna M
Audiol Neurootol 2013;18(6):345-52. Epub 2013 Oct 4 doi: 10.1159/000354158. PMID: 24107406
Destito D, Bucolo S, Florio A, Quattrocchi C
Ear Nose Throat J 2012 Aug;91(8):366-75. PMID: 22930086
Naji M, Zhao C, Welsh SJ, Meades R, Win Z, Ferrarese A, Tan T, Rubello D, Al-Nahhas A
Mol Imaging Biol 2011 Aug;13(4):769-75. doi: 10.1007/s11307-010-0396-8. PMID: 20700766

Diagnosis

Niemeijer ND, Rijken JA, Eijkelenkamp K, van der Horst-Schrivers ANA, Kerstens MN, Tops CMJ, van Berkel A, Timmers HJLM, Kunst HPM, Leemans CR, Bisschop PH, Dreijerink KMA, van Dooren MF, Bayley JP, Pereira AM, Jansen JC, Hes FJ, Hensen EF, Corssmit EPM
Eur J Endocrinol 2017 Aug;177(2):115-125. Epub 2017 May 10 doi: 10.1530/EJE-17-0074. PMID: 28490599
Destito D, Bucolo S, Florio A, Quattrocchi C
Ear Nose Throat J 2012 Aug;91(8):366-75. PMID: 22930086
Naji M, Zhao C, Welsh SJ, Meades R, Win Z, Ferrarese A, Tan T, Rubello D, Al-Nahhas A
Mol Imaging Biol 2011 Aug;13(4):769-75. doi: 10.1007/s11307-010-0396-8. PMID: 20700766

Prognosis

Niemeijer ND, Rijken JA, Eijkelenkamp K, van der Horst-Schrivers ANA, Kerstens MN, Tops CMJ, van Berkel A, Timmers HJLM, Kunst HPM, Leemans CR, Bisschop PH, Dreijerink KMA, van Dooren MF, Bayley JP, Pereira AM, Jansen JC, Hes FJ, Hensen EF, Corssmit EPM
Eur J Endocrinol 2017 Aug;177(2):115-125. Epub 2017 May 10 doi: 10.1530/EJE-17-0074. PMID: 28490599
Piazza P, Di Lella F, Bacciu A, Di Trapani G, Ait Mimoune H, Sanna M
Audiol Neurootol 2013;18(6):345-52. Epub 2013 Oct 4 doi: 10.1159/000354158. PMID: 24107406

Clinical prediction guides

Niemeijer ND, Rijken JA, Eijkelenkamp K, van der Horst-Schrivers ANA, Kerstens MN, Tops CMJ, van Berkel A, Timmers HJLM, Kunst HPM, Leemans CR, Bisschop PH, Dreijerink KMA, van Dooren MF, Bayley JP, Pereira AM, Jansen JC, Hes FJ, Hensen EF, Corssmit EPM
Eur J Endocrinol 2017 Aug;177(2):115-125. Epub 2017 May 10 doi: 10.1530/EJE-17-0074. PMID: 28490599

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