Proliferation index (Ki67) is a powerful predictor of recurrence in pituitary adenoma

Background: Preoperative biochemical diagnosis of acromegaly is based on the determination of the serum levels of insulin-like growth factor 1 (IGF-1) and growth hormone (GH) in the oral glucose tolerance test. In turn, although assumptions concerning the tumour hormonal phenotype may be made on the basis of biochemical tests, the final determination of the exact adenoma profile is possible only on the basis of postoperative immunohistochemical evaluation. Due to the high importance of both – preoperative determination of the concentration of IGF-1 and postoperative immunohistochemical examination of pituitary tumour, the aim of this study was to compare these parameters. Material and methods: The study group consisted of 21 patients with acromegaly and 15 with clinically nonfunctioning pituitary adenoma (CNFPA). In all the patients IGF-1 and prolactin (PRL) concentrations in serum were measured by enzyme–amplified chemiluminescent immunoassay. The immunohistochemical diagnose of the adenoma was achieved with the primary antibodies against the pituitary hormones, the α-subunit and Ki-67 – proliferation indicator. Results: In patients with acromegaly immunohistochemistry besides monohormonal tumours – “pure” somatotropinoma, also somatoprolactinoma and adenoma plurihormonale have revealed. The mean concentrations of IGF-1 were 702, 1480 and 915 ng/mL respectively in each of these groups. In most cases the proliferation index Ki-67 was less than one. In patients with CNFPA, the IGF-1 levels were mostly in reference values and almost in half of cases the Ki–67 value was above one. Conclusions: There are statistically significant differences between preoperative serum IGF-1 concentrations in the somatoprolactinoma group and other adenoma phenotypes in acromegaly patients. This result may suggest the possible link between additional prolactin component with very high concentration of IGF-1 in patients with acromegaly.

Download Full-text

Familial X-Linked Acrogigantism: Postnatal Outcomes and Tumor Pathology in a Prenatally Diagnosed Infant and His Mother

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2019-00817 ◽

2019 ◽

Vol 104 (10) ◽

pp. 4667-4675 ◽

Cited By ~ 5

Author(s):

Brittany K Wise-Oringer ◽

George J Zanazzi ◽

Rebecca J Gordon ◽

Sharon L Wardlaw ◽

Christopher William ◽

...

Keyword(s):

Single Nucleotide Polymorphism ◽

Transcription Factor ◽

Transcription Factors ◽

Pituitary Adenoma ◽

Tumor Cells ◽

Chorionic Villus ◽

Proliferation Index ◽

Stem Cell Markers ◽

Nucleotide Polymorphism ◽

Single Nucleotide

Abstract Context X-linked acrogigantism (X-LAG), a condition of infant-onset acrogigantism marked by elevated GH, IGF-1, and prolactin (PRL), is extremely rare. Thirty-three cases, including three kindreds, have been reported. These patients have pituitary adenomas that are thought to be mixed lactotrophs and somatotrophs. Case Description The patient’s mother, diagnosed with acrogigantism at 21 months, underwent pituitary tumor excision at 24 months. For more than 30 years, stable PRL, GH, and IGF-1 concentrations and serial imaging studies indicated no tumor recurrence. During preconception planning, X-LAG was diagnosed: single-nucleotide polymorphism microarray showed chromosome Xq26.3 microduplication. After conception, single-nucleotide polymorphism microarray on a chorionic villus sample showed the same microduplication in the fetus, confirming familial X-LAG. The infant grew rapidly with rising PRL, GH, and IGF-1 concentrations and an enlarging suprasellar pituitary mass, despite treatment with bromocriptine. At 15 months, he underwent tumor resection. The pituitary adenoma resembled the mother’s pituitary adenoma, with tumor cells arranged in trabeculae and glandular structures. In both cases, many tumor cells expressed PRL, GH, and pituitary-specific transcription factor-1. Furthermore, the tumor expressed other lineage-specific transcription factors, as well as SOX2 and octamer-binding transcription factor 4, demonstrating the multipotentiality of X-LAG tumors. Both showed an elevated Ki-67 proliferation index, 5.6% in the mother and 8.5% in the infant, the highest reported in X-LAG. Conclusions This is a prenatally diagnosed case of X-LAG. Clinical follow-up and biochemical evaluation have provided insight into the natural history of this disease. Expression of stem cell markers and several cell lineage-specific transcription factors suggests that these tumors are multipotential.

Download Full-text

MON-255 Oral Contraceptive Pills Mask an Aggressive Crooke’s Cell Pituitary Adenoma

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.1535 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Helen Prathiba Gnanapragasam ◽

Amrutha Idupuganti ◽

Abhijana Karunakaran

Keyword(s):

Oral Contraceptive ◽

Pituitary Adenoma ◽

Skull Base ◽

Cushing’S Disease ◽

Cushing's Disease ◽

Proliferation Index ◽

Cell Adenoma ◽

Oral Contraceptive Pills ◽

Contraceptive Pills ◽

History Of

Abstract Background Crooke’s cell tumors are rare and aggressive forms of pituitary adenomas. This variant of Cushing’s disease requires prompt diagnosis to avoid life-threatening complications. We report a unique case of Crooke’s cell tumor with longstanding history of irregular menstrual cycles, undiagnosed and later presented as acute unilateral ptosis and diplopia due to aggressive tumor invasion. Clinical Case 23-year-old female presented to the ER with facial swelling, left eye droop and diplopia for 3 days. She had a past medical history of oligomenorrhea and hirsutism which was normalized by oral contraceptive pills (OCP)- a combination of ethinyl estradiol and drospirenone for the last 3 years. Years prior, workup of her oligomenorrhea showed normal androgenic profile with normal DHEA-S, testosterone and 17-OH progesterone. Current exam was also significant for elevated blood pressure 200/110mmHg, BMI 37, pigmented abdominal striae and terminal hair over her chin. Labs remarkable for hypokalemia K+ 2.7 mmol/L (3.5-5.3), elevated AM cortisol 51 mcg/dL (4-20), low TSH 0.152 mcUnit/mL (0.4-5.0), low IGF-1 170 ng/mL (222-566) and FSH 1.4 mUnit/mL (1.0-9.0), with normal prolactin 24.3 ng/mL (<0.5-25) and free T4 0.87ng/dL (0.8-1.8). MRI brain showed 2.8cm homogenous enhancing soft tissue mass involving the central skull base, sphenoid sinus, sella, suprasellar cistern, and parasellar regions; displacing the optic chiasm, and invading the cavernous sinuses bilaterally and orbital apices. Post trans-sphenoidal surgery (TSS) of the pituitary mass, her left eye ptosis and diplopia resolved. Post-op MRI showed subtotal resection of the extra-axial enhancing abnormality at the central skull base with extension to multiple other anatomic spaces. Pathology read consistent with aggressive Crooke’s cell adenoma, showing invasive biologic behavior without an elevated proliferation index with positive ACTH immunohistochemistry supportive of corticotroph cell adenoma. Post-op ACTH level 73 pg/mL (6-50) and cortisol 12.5 mcg/dL (4-20), while on dexamethasone. Repeat TSS was performed for residual adenoma. Cortisol remains elevated at 15.7mcg/dL despite high dose dexamethasone taper by the neurosurgery team for post-op development of right eye ptosis. She is currently awaiting proton beam radiation therapy. Conclusion Crooke’s cell tumors are an aggressive form of pituitary adenoma for which early diagnosis is crucial for its prognosis. Our case highlights the importance of maintaining a wide differential in evaluating young women with menstrual irregularities and to include screening for Cushing’s syndrome. Empiric treatment with OCPs can mask symptoms in the earlier course of Cushing’s disease as in our patient, causing recognition only after presentation with significant tumor growth. Earlier detection could have prevented adenoma invasion and potential neurological sequelae.

Download Full-text

Association of pituitary adenoma with neuronal christoma: A TEM study

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s042482010016889x ◽

1994 ◽

Vol 52 ◽

pp. 232-233

Author(s):

Eva Horvath ◽

Kalman Kovacs ◽

B. W. Scheithauer ◽

R. V. Lloyd ◽

H. S. Smyth

Keyword(s):

Growth Hormone ◽

Pituitary Adenoma ◽

Pituitary Tumor ◽

Nervous Tissue ◽

Alternative Explanation ◽

Growth Hormone Releasing Hormone ◽

Cell Hyperplasia ◽

Releasing Hormone ◽

Secretory Neurons

The association of a pituitary adenoma with nervous tissue consisting of neuron-like cells and neuropil is a rare abnormality. In the majority of cases, the pituitary tumor is a chromophobic adenoma, accompanied by acromegaly. Histology reveals widely variable proportions of endocrine and nervous tissue in alternating or intermingled patterns. The lesion is perceived as a composite one consisting of two histogenetically distinct parts. It has been suggested that the neuronal component, morphologically similar to secretory neurons of the hypothalamus, may initiate adenoma formation by releasing stimulatory substances. Immunoreactivity for growth hormone releasing hormone (GRH) in the neuronal component of some cases supported this view, whereas other findings such as consistent lack of growth hormone (GH) cell hyperplasia in the lesions called for alternative explanation.Fifteen tumors consisting of a pituitary adenoma and a neuronal component have been collected over a 20 yr. period. Acromegaly was present in 11 patients, was equivocal in one, and absent in 3.

Download Full-text