Table 1.

Patients with pituitary adenoma and pheochromocytoma/paraganglioma syndrome (3PAs) with identified germline genetic defects.

		Pituitary				Pheo/PGL
Patient Nr	Sex	Type	Size	Treatment	Age	Type	Treatment	Age	Family history	Mutation	LOH/ICH in PA	Reference
1	F	PRL	NK	NK	27	Pheo	NK	NK	No	SDHA c.91C > T p.Arg31Ter, VHL c.589G > A p.Asp197Asn	Not performed	Dénes et al. (2015) [22]
2	F	PRL	Macro	NK	49	PGLs	NK	49	NK	SDHA p.Arg31 * c.91C > T	SDHA/SDHB negative staining	Niemeijer et al. (2015) [13]
3	M	GH	Macro	SSA	84	PGL	No	84	No	SDHAF2 c.−52T > C	Not performed	Dénes et al. (2015) [22]
4	M	PRL	Macro	DA, surgery	33	PGL	Surgery	33	Mother: PRL, brother: PGL	SDHB c.298 T > C p.Ser100Pro	LOH at SDBH locus, intracytoplasmic vacuoles	Dénes et al. (2015) [22]
5	F	NFPA	Macro	Surgery x3, RT	53	PGL	RT	28	Sister: glioma	SDHB c.587 G > A p.Cys196Tyr	LOH at SDBH locus/SDHB staining: diffuse/intracytoplasmic vacuoles	Dénes et al. (2015) [22]
6	F	PRL	Macro	DA	38	PGLs carotid and mediastinal	Carotid: surgery, mediastinal: inoperable	35	Brother PGLs	SDHB mutation, (actual genetic defect not available)	Not performed	Gorospe et al. (2017) [76]
7	F	PRL	Macro	DA, RT	60	PGL	RT	60	NK	SDHB c.423 + 1 G > A	Not performed	Dénes et al. (2015) [22]
8	F	NFPA	Micro	No	50	Pheo	Surgery	50	NK	SDHB c.770dupT p.Asn-258GlufsTer17	Not performed	Dénes et al. (2015) [22]
9	M	GH	NK	SSA	72	PGL	No	70	Brother & niece: PA, sister: bilateral HNPGL	SDHB c.689 G > A p.Arg230His	Not performed	Xekouki et al. (2015) [26]
10	F	PRL	Micro	NK	50	PGL	NK	47	Brother: HNPGL, grandmother: GIST	SDHB c.642 + 1 G > A, splice site alteration	Not performed	Xekouki et al. (2015) [26]
11	F	PRL	Micro	DA	33	PGL	Surgery	43	Brain tumor	SDHB c.18 C > A p.Ala6Alaa 3 PTEN polymorphisms	Not performed	Efstathiadou et al. (2014) [77]
12	F	PRL	Macro	DA	38	PGL	SSA	NK	Brother index case: PGL. Mother and sister positive for region of ex.1 of SDHB	deletion affecting ex. 1 of SDHB	Not performed	Guerrero Pérez et al. (2016) [21]
13	M	PRL	Macro	DA	53	PGL	Surgery	38	Cousin: PA, brother: PGL	SDHC c.380 A > G p.His127Arg	Not performed	Dénes et al. (2015) [22]
14	F	PRL	Macro	NK	60	PGL	NK	60	No	SDHC c256–257insTTTp-Phe85dup	Not performed	López-Jiménez et al. (2008) [78]
15	F	PRL	Macro	Surgery, DA	23	PGL	Surgery	32	Sister, aunt and grandmother: PA; sister: bilateral HNPGL	SDHD c.242 C > T, p.Pro81Leu	Not performed	Xekouki et al. (2015) [26]
16	M	PRL	Macro	DA, surgery	60	PGL, Pheo	Surgery (Pheo)	62	NK	SDHD c.274 G > T pAsp92Tyr	LOH at SDHD locus/SDHB positive ICH, SDHA IHC positive	Papathomas et al. (2014) [25]
17	F	GH	Macro	Surgery, SSA	56	PGL	NK	56	Father and 2 sisters: HNPGL; sister: GIST	SDHD c.274 G > T p.Asp92Tyr	LOH at SDHD locus/SDHB positive ICH, SDHA IHC positive	Papathomas et al. (2014) [25]
18	F	PRL	Macro	DA, surgery	33	PGL	Surgery x2	39	Aunt, uncle, brother: HNPGL	SDHD c.242 C > T p.Pro81Leu	Not performed	Varsavsky et al. (2013) [79]
19	M	GH	Macro	SSA, surgery	37	PGL, Pheo	Surgery	37	Sister and paternal uncle neck PGLs HNPGL	SDHD c.298_301 del, premature stop at codon 133 AIP & CDKN1B polymorphism	PA: LOH at SDHD locus, reduced SDHD protein/patchy SDHB staining	Xekouki et al. (2012) [15,17]
20	M	GH/PRL	Macro	Surgery, RT, DA	27	Pheo	Surgery	31	No	MEN1 c.1452delGp.Thr557Ter	Menin staining of the Pheo: no menin positive cells	Dénes et al. (2015) [22]
21	F	NFPA	Macro	Surveillance	45	PGL	NK	45	No	MEN1 c.196_200dupAG-CCC frameshift (pathogenic), polymorphism C423T no amino acid change	Not performed in Pheo	Jeong et al. (2014) [80]
22	M	PRL	NK	NK	41	Pheo	Surgery	48	NK	MEN1 K119X, RET WT	Not performed in Pheo	Langer et al. (2002) [81]
23	NK	NK	NK	NK	NK	Pheo	NK	NK	Hyperparathy-roidism and pancreatic islet cell tumor	MEN1 c.320dell2	Not performed in Pheo	Dackiw et al. (1999) [32]
24	NK	NK	NK	NK	NK	Pheo	NK	NK	Pancreatic islet cell tumor and rectal leiomyoma	MEN1 1325insA	Not performed in Pheo	Dackiw et al. (1999) [32]
25	M	PRL	NK	NK	29	Pheo	NK	32	MEN1	Not performed, other family members MEN1 mutation	HPTH at age 21 years	Carty et al. (1998) [82]
26	M	GH	Macro	Surgery	62	Pheo	Surgery	62	No	RET p.Cys618Ser	Not performed in PA	Heinlen et al. (2011) [83]
27	M	ACTH	Micro	Surgery x2	48	Pheo	Surgery	66	Son: HPTH	RET c.1900T > C, p.Cys634Arg. Negative for MEN1 mutations	Not performed in Pheo	Naziat et al. (2013) [84]
28	F	PRL	Macro	DA	49	Pheo	Bilateral adrenalectomy	49	No	MAX c.296 G > T, Neg for MEN1, VHL, SDHB, SDHC, SDHD, SDHAF2, or TMEM127 genes	Not performed	Roszko et al. (2017) [34]
29	M	PRL	Micro	DA	49	Pheo	Surgery	32	No	Germinal heterozygous deletion of exon 3 of MAX (detected by MLPA). Neg for RET, VHL, SDHx, CDKN1B, AIP, MEN1	Not performed	Daly et al., (2018) [33]
30	F	GH	Macro	SSA, DA, Pegvisomant, RT	26	Bilateral Pheos	Bilateral adrenalectomy	35	No	Germinal heterozygous deletion of exons 1–3 and intron 3 of MAX. Neg for RET, VHL, SDHx, CDKN1B, AIP, MEN1	Not performed	Daly et al. (2018) [33]
31	M	GH	Macro	Surgery, RT	16	Bilateral Pheos	Bilateral adrenalectomy	22	No	Germinal heterozygous deletion of exon 3 of MAX (detected by MLPA). Neg for RET, VHL, SDHx, CDKN1B, AIP, MEN1	Not performed	Daly et al. (2018) [33]

M: Male; F: Female; NFPA: Non-functional pituitary adenoma; PRL: Prolactinoma; GH: Acromegaly; Macro: Macroadenoma; Micro: Microadenoma; DA: Dopamine agonist; RT: Radiotherapy; SSA: Somatostatin analogue; Pheo: Pheochromocytoma; PGL: Paraganglioma; HNPGL: Head and neck paraganglioma; PTC: Papillary thyroid cancer; GIST: Gastrointestinal stromal tumor; pNET: Pancreatic neuroendocrine tumor; MTC: Medullary thyroid carcinoma; HPTH: Hyperparathyoidism; NK: Not known; MEN1: Multiple endocrine neoplasia type 1; NF1: Neurofibromatosis type 1; A: Single nucleotide polymorphism with a minor allele frequency of 0.2% and a genotype frequency of 0.5% (1000 Genomes Project Consortium, 2012) [85].