Pituitary stalk duplication (PSD) is a rare congenital anomaly characterized by the abnormal development of the pituitary stalk, while often associated with other midline defects and pituitary gland duplication [1]. Isolated PSD is an extremely rare condition with limited case reports in the literature [1-5]. Patients may present with a diverse range of neurological, endocrinological, and ophthalmological symptoms.

Magnetic resonance imaging (MRI) of the sella turca remains the gold standard for diagnosing this condition. (1). Due to its rarity, it can be challenging to differentiate isolated PSD from other sellar lesions, particularly metastatic disease.

The pituitary fossa is an uncommon site for metastatic tumor spread. Breast and lung cancers are the primary tumors metastasizing to the pituitary, with breast cancer, especially HER2-positive tumors [6,7]. Radiologically, metastatic sellar lesions often involve structures like the pituitary stalk, cavernous sinus, and diaphragma sellae [8], differentiating them from isolated PSD.

The precise etiology of PSD remains elusive, but a complex interplay of genetic and signaling pathways is likely involved [9,10]. Recent genetic studies have implicated specific genes in the pathogenesis of isolated PSD, suggesting a genetic basis for this rare condition [4,11].

This case report presents a 64-year-old female who initially presented with a sellar lesion that was misdiagnosed as a metastatic brain tumor from her HER2-positive breast cancer. However, further investigation revealed an isolated PSD. This case underscores the importance of considering PSD in the differential diagnosis of sellar lesions, especially in cases where initial imaging suggests pathologies like pituitary metastasis.

Patient Information

A 64-year-old female presented with a “supposed” metastatic brain lesion detected via MRI of the brain, alongside complaints of hair loss, insomnia, and headache. The patient had no symptoms of polyuria or polydipsia. Her family history is notable for Crohn’s disease, gastric ulcer, myelodysplasia, bowel cancer (mother), and acromegaly (cousin). She was diagnosed with Crohn’s disease at age 12 and with HER2-positive breast cancer at age 25, for which she underwent surgery and chemotherapy. At age of 40 she entered menopause and in 2022 developed a pulmonary nodule.

Clinical Findings

On physical examination, the patient’s height was 158cm, weight 71kg, with a blood pressure of 152x102 mmHg, and heart rate of 102 beats per minute. Neurological examination showed no pathological findings.

Diagnostic Assessment

In 2022, during an oncology evaluation, brain MRI revealed a breast cancer metastatic lesion in the pituitary stalk — a regular expansive lesion measuring 1.5 x 0.9 x 0.8 cm - affecting the entire pituitary stalk, extending to the superior adenohypophysis, and involving the optic chiasm (Figure 1A). Subsequent biochemical investigations (Table 1) were performed. Further imaging, specifically MRI scans of the sella turca, identified an enlargement in the hypothalamic infundibular region with apparent pituitary stalk

Table 1: Biochemical test results.

This case report describes a rare instance of isolated PSD, incidentally identified during a brain MRI in a 64-year-old female with HER2-positive breast cancer. Notably, the MRI revealed a secondary lesion affecting the pituitary stalk, with PSD confirmed upon further imaging, without associated abnormalities. Despite a complex medical history, the patient exhibited no signs of hormonal dysfunction. This incidental finding underscores the importance of careful radiological evaluation and recognition of this anomaly, even in asymptomatic patients.

Pituitary gland metastasis is a rare but clinically significant condition that can pose diagnostic and therapeutic challenges. While primary pituitary tumors are more common lung and, particularly, HER2-positive breast cancers are common primary tumor sites for metastatic lesions in the sellar region [6]. Clinical manifestations can include diabetes insipidus, hypopituitarism, headache, visual disturbances, and ophthalmoplegia, often resulting from mass effect on surrounding structures [12]. Imaging features can help differentiate metastatic lesions from primary pituitary tumors. Metastatic lesions may exhibit pituitary stalk thickening, cavernous sinus involvement, and diaphragma sellae constriction [8]. In contrast, isolated PSD typically presents with a distinctive imaging appearance, characterized by a duplicated pituitary stalk without other sellar abnormalities. Our case initially presented as a suspected secondary lesion but was ultimately confirmed as an isolated PSD upon a second MRI of the sella turca. A thorough patient history, comprehensive laboratory testing of the hypothalamic-pituitary-gonadal axis, and careful image analysis are essential for accurate diagnosis.

Isolated PSD is a rare anomaly with a limited number of cases documented in the literature [1-5]. This condition is often associated with other midline defects, such as craniofacial anomalies, hypopituitarism, hyperprolactinemia, deficient GH(growth hormone) secretion and diabetes insipidus [1]. In our case the patient presents no endocrine dysfunction or pituitary gland abnormalities. This case highlights the potential for isolated PSD in adults without significant clinical consequences.

Several case reports have described various associations of PSD, including genetic factors. For instance, a heterozygous deletion of chromosome 14, encompassing the Thyroid Transcription Factor-1 (TTF-1) gene, has been linked to PSD and associated thyroid dysfunction [4]. Additionally, familial mutations in the ROBO1 gene have been implicated in PSD, often presenting with ectopic posterior pituitary and anterior pituitary hypoplasia [11]. In contrast, our patient exhibited isolated PSD without any endocrine dysfunction or anatomical alterations in the pituitary gland. This unique presentation highlights the diverse clinical spectrum of PSD, ranging from syndromic to isolated forms, and underscores the importance of individual assessment.

PSD is increasingly recognized as a contributor to midline developmental anomalies. It can manifest in various ways, including vascular, ocular, and endocrine abnormalities. Khodeiry et al [13] linked isolated PSD to morning glory disc anomaly and moyamoya disease, while Loddenkemper et al [14] also reported this association. In more complex cases, PSD can lead to significant neurological and endocrine deficits. For instance, patients with isolated PSD with, pituitary adenoma, and aqueductal stenosis or intrasellar dermoid cyst and third ventricle herniation may present with hypopituitarism (2,3). Additionally, Alkhyeli et a [15]. reported a case of isolated PSD associated with primary empty sella syndrome and severe hyponatremia. In the pediatric population, Sravya et al [1] found an association between isolated PSD and short stature. While our patient did not present with any endocrinological, vascular, or ocular abnormalities, this case underscores the need for a comprehensive evaluation of patients with isolated PSD, as the clinical presentation can be variable and may involve multiple systems.

The pathogenesis of PSD remains unclear, though it is likely to involve disruptions in embryological development. The pituitary gland and stalk develop begins on the 22nd day postgestation, anterior to the notochord, separated by the prochordal plate. The gland forms as a single entity from neural ectoderm, not from two distinct primordia

[14]. The infundibulum develops into the pituitary stalk and this is orchestrated by signaling pathways such as Sonic Hedgehog (Shh), which promotes the growth and differentiation of progenitor cells in the hypothalamus and pituitary regions (9,10). Hypotheses have been proposed to explain the mechanism of PSD, including notochord splitting due to mechanical forces, duplication of the prochordal plate, aberrant ectodermal adhesion, and duplication of prochordal plate or notochordal process cells [3]. Therefore, embryological development appears to play a critical role in the pathogenesis of PSD, particularly signaling pathways and cellular mechanisms.

A limitation of this case was the lack of genetic investigation. However, several reports suggest a potential genetic and developmental basis for pituitary stalk duplication (PSD) [4,11]. While PSD may be a congenital anomaly in some cases, it can also be an incidental finding, as demonstrated in our patient, and may not always require specific treatment.

PSD is often associated with other developmental anomalies and endocrine dysfunction, our case highlights the importance of early recognition, thorough imaging, and careful monitoring, especially in patients with complex medical histories. Although the clinical implications of pituitary stalk duplication are still not fully understood, this case suggests that it can occur without significant endocrine disturbances, at least in the short term.

Further studies are needed to clarify the potential long-term consequences of this condition and to better define the management strategies for patients with isolated pituitary stalk duplication.

Funding: No funding was received for this research.

Acknowledgments: The authors declare no conflict of interest.

1. Sravya SL, Swain J, Kanwar JB, Sahoo AK, Mangaraj S, Jadhao P, et al. Pituitary stalk duplication: A radiological surprise in a child with short stature. AACE Clin Case Rep. 2023; 9: 166-169.
2. Madhusudhan KS, Kandpal H. Pituitary stalk duplication with intrasellar dermoid and herniation of the third ventricle. Pediatr Radiol. 2009; 39: 1013.
3. Petridis AK, Barth H. Pituitary stalk duplication in ventral-dorsal direction in a patient with pituitary gland adenoma and aqueductal stenosis. Clin Anat. 2010; 23: 879-880.
4. Accornero S, Danesino C, Bastianello S, D Errico I, Guala A, Chiovato L. Duplication of the pituitary stalk in a patient with a heterozygous deletion of chromosome 14 harboring the thyroid transcription factor-1 gene. J Clin Endocrinol Metab. 2010; 95: 3595-3596.
5. Ozdemir M, Kavak RP, ?im?ir BD, Akdag T, Guldogan Isolated pituitary stalk duplication. Eur Clin Anal Med. 2020.
6. Schill F, Nilsson M, Olsson DS, Ragnarsson O, Berinder K, Eden Engstrom B, et al. Pituitary metastases: A nationwide study on current characteristics with special reference to breast J Clin Endocrinol Metab. 2019; 104: 3379-3388.
7. Shimon I. Metastatic spread to the pituitary. Neuroendocrinology. 2020; 110: 805-808.
8. Kameda-Smith MM, Zhang E, Lannon M, Algird A, Reddy K, Lu JQ. Pituitary metastasis: From pathology to clinical and radiological considerations. J Clin Neurosci. 2021; 93: 231-240.
9. Goto M, Hojo M, Ando M, Kita A, Kitagawa M, Ohtsuka T, et Hes1 and Hes5 are required for differentiation of pituicytes and formation of the neurohypophysis in pituitary development. Brain Res. 2015; 1625: 206-217.
10. Fu T, Towers M, Placzek MA. Fgf10+ progenitors give rise to the chick hypothalamus by rostral and caudal growth and differentiation. Development. 2017; 144: 3278-3288.
11. Scala M, Accogli A, Allegri AME, Tassano E, Severino M, Morana G, et Familial ROBO1 deletion associated with ectopic posterior pituitary, duplication of the pituitary stalk and anterior pituitary hypoplasia. J Pediatr Endocrinol Metab. 2019; 32: 95-99.
12. Angelousi A, Alexandraki KI, Kyriakopoulos G, Tsoli M, Thomas D, Kaltsas G, et al. Neoplastic metastases to the endocrine glands. Endocr Relat Cancer. 2020; 27: R1-R20.
13. Khodeiry MM, Chau VQ, Yasin A, Starke RM, Miri S, Pasol J. Morning glory disc anomaly associated with moyamoya disease and pituitary stalk Am J Ophthalmol Case Rep. 2022; 27: 101632.
14. Loddenkemper T, Friedman NR, Ruggieri PM, Marcotty A, Sears J, Traboulsi EI. Pituitary stalk duplication in association with moya moya disease and bilateral morning glory disc anomaly - broadening the clinical spectrum of midline defects. J Neurol. 2008; 255: 885-890.
15. Alkhyeli F, Boharoon H, Almarzouqi A. Severe hyponatremia in a 46-year-old female with pituitary stalk duplication and primary empty sella syndrome. Cureus. 2023; 15: e43851.