Somatotroph pituitary adenoma with acromegaly and autosomal dominant polycystic kidney disease: SSTR5 polymorphism and PKD1 mutation

Abstract

A 39-year-old woman with autosomal dominant polycystic kidney disease (ADPKD) presented with acromegaly and a pituitary macroadenoma. There was a family history of this renal disorder. She had undergone surgery for pituitary adenoma 6 years prior. Physical examination disclosed bitemporal hemianopsia and elevation of both basal growth hormone (GH) 106 ng/mL (normal 0–5) and insulin-like growth factor (IGF-1) 811 ng/mL (normal 48–255) blood levels. A magnetic resonance imaging scan disclosed a 3.0 cm sellar and suprasellar mass with both optic chiasm compression and left cavernous sinus invasion. Histologic, immunohistochemical and ultrastructural studies of the lesion disclosed a sparsely granulated somatotroph adenoma. Standard chromosome analysis on the blood sample showed no abnormality. Sequence analysis of the coding regions of PKD1 and PKD2 employing DNA from both peripheral leukocytes and the tumor revealed the most common PKD1 mutation, 5014_5015delAG. Analysis of the entire SSTR5 gene disclosed the variant c.143C>A (p.L48M, rs4988483) change in the heterozygous state in both blood and tumor, while no pathogenic mutations were noted in the MEN1, AIP, p27Kip1 and SSTR2 genes. To our knowledge, this is the fourth reported case of a GH-producing pituitary adenoma associated with ADPKD, but the first subject to extensive morphological, ultrastructural, cytogenetic and molecular studies. The question arises whether the physical proximity of the PKD1 and SSTR5 genes on chromosome 16 indicates a causal relationship between ADPKD and the somatotroph adenoma.

A Rare Case of Acromegaly and Autosomal Dominant Polycystic Kidney Disease: Case Report and Brief Review of Literature

“…In the overwhelming majority (over 90% of patients), acromegaly is caused by a GH-secreting pituitary adenoma (9). The association of acromegaly with ADPKD is very rare and to the best of our knowledge only 4 such cases have been described previously (3)(4)(5)(6). In all of these reported cases, pituitary tumors in ADPKD patients were functional GHsecreting ones.…”

“…Hence, the authors suspected a potentially beneficial effect of octreotide on progression of renal cyst size in ADPKD patients. Lastly, Syro et al (6) reported the case of a 39-year-old female suffering from acromegaly due to GH-secreting pituitary macroadenoma and ADPKD. The authors had done extensive hormonal, molecular, and histologic work-up of this particular case.…”

“…On the other hand, autosomal dominant polycystic kidney disease (ADPKD) is an inherited disorder caused by mutations in the PKD1 and PKD2 genes resulting in classical renal and extrarenal manifestations (1,2). The association of ADPKD with acromegaly is very rare and to the best of our knowledge only 4 such cases have been reported in the literature (3)(4)(5)(6). We report a case of a 42-year-old woman with acromegaly and ADPKD with a brief review of literature.…”

The Genetics of Pituitary Adenomas

“…Finally, few patients with diagnosis of PA and additional genetic syndromes have been reported in the literature, for example, a patient with Beckwith-Wiedemann syndrome (loss of methylation of imprinting critical region 2 on chromosome 11p) and ACTH-secreting adenoma, two family members with Cantu syndrome (ABCC9) and non-functioning adenomas, a patient with autosomal dominant polycystic kidney disease (PKD1) and acromegaly, and a patient with X-linked adrenal hypoplasia (due to a DAX1 defect) and ACTH-secreting adenoma [97][98][99][100]. The etiologic association of the pathogenesis of PA with the identified germline genetic defect is not confirmed in most of them, however, potential relationship cannot be excluded.…”

A differential diagnosis of inherited endocrine tumors and their tumor counterparts

“…After the AIP discovery, IFS cases have been referred to as FIPA (26,174). Interestingly, familial somatotropinoma leading to acromegaly/gigantism may also occur in the context of other IET syndromes, such as MEN1, CS, and autosomal dominant polycystic kidney disease (178,179). …”