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Diagnosis and monitoring of an incidental infundibular lesion
A 61-year-old male was referred to the endocrine clinic for evaluation of a pituitary mass. A head MRI was ordered for the complaint of decreased smell for 2 years. The patient also had symptoms of reduced libido and sexual dysfunction.
Review of systems was negative for symptoms of frequent urination, fatigue, orthostatic dizziness, visual field defects and headaches.
Poorani Goundan
Stephanie L. Lee
Mass lesion
The head MRI showed a heterogeneously enhancing mass lesion measuring 7.6 mm (transverse) by 9.4 mm (cranial-caudal) by 7.9 mm (anteroposterior) along the anterior aspect of the pituitary stalk, causing mild mass effect on the optic chiasm (Figures 1 and 2B).
His endocrine evaluation was normal:
- Prolactin 8.4 ng/mL (normal, 2.1-17.7 ng/mL);
- Thyroid-stimulating hormone 0.5 uIU/mL (normal, 0.35-5.5 uIU/mL);
- Free thyroxine 1.08 ng/dL (normal, 0.89-1.8 ng/dL);
- Adrenocorticotropic hormone (ACTH) 22 pg/mL (normal, 7-50 pg/mL);
- Cortisol 6.3 mcg/dL (normal, 5-23 mcg/dL);
- Total testosterone 562 ng/dL (normal, 241-827 ng/dL);
- Follicle-stimulating hormone (FSH) 5.5 mIU/mL (normal, 1.6-19.1 mIU/mL);
- Luteinizing hormone (LH) 4.4 mIU/mL (normal, 1.5-9.3 mIU/mL);
- Insulin-like growth factor I 51.3 ng/mL (normal, 75-228 ng/mL);
- Serum osmolality 287 mOsm.kg (normal, 275-295 mOsm/kg);
- Urine osmolality 543 mOsm/kg (normal, 50-1200 mOsm/kg);
- Sodium 139 mmol/L (normal, 135-145 mmol/L);
- Potassium 4.3 mmol/L (normal, 3.5-5.1 mmol/L).
Visual field testing was performed, but the patient was unable to perform the test, making the results unreliable.
Figure 1. MRI of the sella. A. Transverse B. Traverse + gadolinium. C. Sagittal. D. Sagittal + gadolinium. The anterior pituitary (AP) is normal (green arrow). There is mass measuring 7.6 mm (transverse) x 9.4 mm (cranial caudal) x 7.9 mm (AP) with heterogeneously enhancement after gadolinium contrast. The mass (red mass) is located in the anterior aspect of the pituitary stalk causing a minimal mass effect on the left side of the optic chiasm (OC). The pituitary stalk enhances and can be seen posterior to the mass (blue arrow).
Reprinted with permission from: Stephanie L. Lee, MD, PhD.
Although neurosurgery recommended biopsy, the patient and the endocrinologist decided on “watchful waiting” with serial clinical evaluation, biochemical testing and imaging. It was felt that his complaints of anosmia and reduced libido were not caused by endocrine dysfunction or the pituitary stalk mass. After an 8-year follow-up, his anterior and posterior pituitary function remain normal and the mass has not grown on repeat magnified and fine-cut MRI imaging of the sella.
Anterior, posterior pituitary
The pituitary gland (Figure 2A) is composed of two parts of different embryologic origin: the adenohypophysis (anterior pituitary) and neurohypophysis (posterior pituitary). The adenohypophysis develops from an upward invagination of the oral ectoderm, called the Rathke’s pouch. Eventually, the Rathke’s pouch completely separates from the oral epithelium and develops into the anterior pituitary.
The posterior pituitary arises from the downward extension of neural ectoderm from the floor of the diencephalon. The axons of the magnocellular neuron bodies originating in the hypothalamic supraoptic and paraventricular nuclei extend through the pituitary stalk (infundibulum) to terminate in the posterior pituitary. Injuries to the axons in the pituitary stalk will cause vasopressin deficiency and diabetes insipidus.
The parvocellular neuron axons from other hypothalamic nuclei terminate in the median eminence (Figure 2) and secrete pituitary hormone-releasing factors into a venous portal plexus. The venous plexus surrounds the infundibulum and transports the releasing factors down the pituitary stalk to regulate the anterior pituitary hormone secretion.
Figure 2. Diagram of the hypothalamus, pituitary stalk, posterior pituitary (PP) and anterior pituitary (AP). The cell bodies of the ADH secreting magnocellular neurons (green) are in the hypothalamus with the axons extending through the pituitary stalk (infundibulum, red arrow) and ending in the posterior pituitary (neurohypophysis). The hypothalamic factors are synthesized in small (parvocellular) neurons that terminate in the median eminence (purple arrow) where the hypothalamic factors are secreted into the capillary venous plexus. The venous plexus (pink arrows) descends along the pituitary stalk to deliver the factors to the anterior pituitary to regulate pituitary hormone secretion from the anterior pituitary (adenohypophysis) Note: the drawing is not drawn to scale. A. Normal anatomy. B. Mass sitting in the anterior pituitary stalk.
Injury to the stalk interrupts the transport of these factors, resulting in insufficiency of all the anterior pituitary hormone except prolactin, whose secretion is increased. Stalk injury reduces the putative prolactin-inhibiting factor from reaching the anterior pituitary, resulting in an increase in prolactin secretion.
The pituitary stalk tapers superiorly (cranial) to inferiorly (caudal) and measures 3.3 mm at the level of the optic chiasm and 1.9 mm at its site of insertion into the pituitary gland. The normal infundibular stalk shows a lower signal intensity compared with the optic chiasm and neurohypophysis on T1-weighted MRI images. Due to the absence of a blood-brain barrier, the stalk and anterior pituitary enhances after contrast administration.
Challenges of imaging
Hamilton evaluated 65 children and adults with pituitary stalk lesions and showed that in adults, the most common infundibular pathologies were 44% inflammatory, 36% neoplasm, and 20% were developmental defects.
Lymphocytic infundibuloneurohypophysitis (stalk and posterior pituitary) is the most common inflammatory cause of pituitary stalk lesions and presents as an enhancing thickening of the stalk. It is considered to be an autoimmune process and often associated with idiopathic central diabetes insipidus. Central diabetes insipidus in a patient younger than 30 years with a history of other autoimmune diseases and a thickened pituitary stalk on MRI imaging is most likely to be due to infundibuloneurohypophysitis.
Granulomatous diseases, including sarcoidosis, Wegener’s granulomatosis and tuberculosis, may cause pituitary stalk thickening. Langerhans cell histiocytosis, which is primarily seen in children, can involve the hypothalamus and infundibulum. Between 5% and 50% of these patients have diabetes insipidus.
Infundibular tumors can either be due to metastatic or primary brain tumors. Germinomas involving the stalk can occur in children and adults. It is the most common tumor in children presenting with diabetes insipidus. In the case series by Hamilton, metastases was the most common infundibular neoplasms in adults. Other tumors in the pituitary stalk include leukemia, lymphoma, gliomas (astrocytoma, ependymomas and pleomorphic xanthoastrocytomas) and pituicytomas (anterior pituitary adenomas).
An infundibular lesion needs to be evaluated with imaging and biochemical testing for both anterior and posterior pituitary function. The best imaging modality is a magnified MRI view of the pituitary, stalk and hypothalamus without and with gadolinium contrast administration.
If optic chiasm involvement is suspected, formal visual field testing is required. Hormonal evaluation should include testing for diabetes insipidus by checking serum and urine osmolality and evaluation of the anterior pituitary function with prolactin, IGF-I, TSH, free T4, ACTH, cortisol, LH and FSH levels. Cerebrospinal fluid (CSF) analysis can be done to check for the germinoma tumor marker, human chorionic gonadotropin (hCG). Given the difficulty and risk associated with pituitary stalk biopsy, it should be considered only when CSF analysis is positive for tumor markers or if there is increase in size seen on serial imaging.
Simmons GE. Am J Roentgenol. 1992;159:375-377.
Stephanie L. Lee, MD, PhD, ECNU, is an Associate Professor of Medicine and Associate Chief, in the Section of Endocrinology, Diabetes and Nutrition at Boston Medical Center. Lee can be reached at Boston Medical Center, 88 E. Newton St., Endocrinology Evans 201, Boston, MA 02118; email: stephanie.lee@bmc.org. She reports no relevant financial disclosures.
Poorami Goundan, MD, is a fellow at Boston Medical Center. She reports no relevant financial disclosures.