TABLE 1B.
Studies with young (≤30 years) sporadic pituitary adenoma patients.
| References | Population | No. of sporadic patientsa | Subtype adenoma | Investigated genes | Prevalence of mutationsb | Possible predictorsc | |
|---|---|---|---|---|---|---|---|
| Cohort | Additional selection criteria | ||||||
| Georgitsi et al. (43) | Italy | Age at disease onset or diagnosis <18 years Exclusion of family history of MEN1 |
36d | GH = 5 PRL = 19 ACTH = 3 NFPA = 7e GH/PRL = 2 |
AIP | 2.8% (1 pt) | N/A (1 case) |
| Stratakis et al. (44) | USA (Bethesda) | Age at diagnosis ≤18 years AND (1) Cushing disease or (2) GH/PRL secreting PA |
80 | GH = 3 PRL = 3 ACTH = 74 |
AIP, MEN1, CDKN1B, CDKN2C, PRKAR1A |
AIP: 3.8% (3 pt) MEN1: 1.3% (1 pt) |
N/A (4 cases) |
| Tichomirowa et al. (26) | Internationalf | Age at diagnosis <30 years Macroadenoma (≥10 mm on MRI) |
163 | GH = 83 PRL = 61 ACTH = 2 TSH = 1 NFPA = 16g |
AIP | 11.7% (19 pt) | Younger age Extrasellar extension Male gender |
| Cuny et al. (13) | France | Age at diagnosis <30 years Macroadenoma (≥10 mm on MRI) Exclusion of patients with hypercalcemia |
174h | GH = 79 PRL = 74 ACTH = 8 TSH = 1 NFPA = 12i |
AIP, MEN1 |
AIP: 8.6% (15 pt) MEN1: 3.4% (6 pt) |
Younger age
(AIP & MEN1) Extrasellar extension (AIP) Gigantism (AIP) Male gender (AIP) NFPA (AIP) Prolactinoma (MEN1) |
| Schöfl et al. (36)j | Germany | Acromegaly Age at diagnosis <30 years |
87 | GH = 87 | AIP | 2.3% (2 pt) | N/A (2 cases) |
| Hernandez-Ramirez et al. (45) | International | Age at disease onset ≤30 years | 404k | GH = 290 PRL = 67 ACTH = 21 TSH = 2 NFPA = 21l Other = 3m |
AIP, MEN1, CDKN1Bn |
AIP: 8.4% (34 pt) MEN1: 0 CDKN1B: 0 |
Younger age Macroadenoma Extrasellar extension Gigantism GH secreting PA |
N/A, not applicable; MEN1, multiple endocrine neoplasia type 1; PA, pituitary adenoma; pt, patients.
GH, somatotroph adenoma; PRL, lactotroph adenoma; ACTH, corticotroph adenoma; TSH, thyrotroph adenoma; NFPA, non-functioning pituitary adenoma; GH/PRL, mixed somatotroph/lactotroph adenoma.
Cursive predictors: suggestive predictor but no statistical significance reached/insufficient data to calculate statistical significance.
Only (groups of) patients are included of which the sporadic status could be determined.
Mutations or variants that were considered pathogenic or likely pathogenic by the authors of each study.
Possible predictors are presented if a minimum of five cases of patients with a germline mutation are reported.
Three patients previously reported in Georgitsi et al. (46).
Adenoma subtype is based on “clinical diagnosis”.
Belgium, Brazil, Bulgaria, Czech Republic, France, Germany, Italy, Lebanon, and Spain.
Definition of NFPA is not provided. The tumor of the only NFPA patient with a germline AIP mutation was negative for all pituitary hormones on immunohistochemistry.
Fifty-nine patients previously reported in Tichomirowa et al. (26).
Definition of NFPA is not provided. The tumor of one NFPA patient with a germline AIP mutation had a partial (50%) immunoreactivity for GH without any pituitary hormonal hypersecretion in vivo (silent somatotroph adenoma). The tumors of the other three NFPA patients with a germline AIP or MEN1 mutation were non-reactive on immunostaining experiments.
This study is also presented in Table 1A.
Six patients previously reported in Leontiou et al. (32).
Definition of NFPA is not provided. Immunohistochemistry results were available in 103 (out of 404) patients. All sporadic patients with a germline AIP mutation and available histopathology results (n = 14) had GH positive pituitary adenomas by immunohistochemistry. In the group of sporadic patients with available histopathology results but without germline AIP mutation (n = 89), three tumors were non-reactive (null cell PA).
One FSH-secreting PA, two not specified.
MEN1 gene analysis is performed in 33 patients, CDKN1B gene analysis is performed in one patient.