Introduction

Rathke's cleft cysts (RCCs) are uncommon, non-neoplastic cysts in the sellar or suprasellar region, typically lined by columnar or ciliated cuboidal epithelium with goblet cells. Small RCCs are usually asymptomatic and detected incidentally, whereas larger ones can lead to pituitary dysfunction, panhypopituitarism, or visual problems from optic chiasm compression.[1] Polyorchidism is a rare congenital condition involving extra testes, usually three. These are often found incidentally during evaluation of other inguinoscrotal conditions like hernias or varicoceles. [2]

RCCs and polyorchidism arise from distinct embryological tissues and their simultaneous occurrence has not been previously documented in the literature. This report describes a 58-year-old male with panhypopituitarism caused by a symptomatic RCC and incidental quadricorchism, underscoring the value of thorough evaluation and interdisciplinary care. Their simultaneous occurrence may indicate developmental anomalies and highlight the importance of considering rare combinations in diagnosis.

The risk of malignancy in individuals with multiple testes is due to the possibility that a second, separate tumor may occur in the remaining testicle. This is a rare but documented event that can be influenced by factors such as early diagnosis of the first tumor, reduced testicular volume, or a history of undescended testes (cryptorchidism). Second, RCC may recur after surgical intervention. This necessitates long term follow up for both conditions. [3]

Case Report

A 58-year-old man presented with altered consciousness, severe hypoglycemia, hypotension, and bradycardia. He was treated with glucose, hydrocortisone, and supportive care. After stabilization, he reported intermittent right upper abdominal pain, vomiting, low libido for three years, and a history of drug abuse. Exam revealed right hypochondrium tenderness, sparse pubic and axillary hair, small testes, and two additional palpable masses; he has two children.

The clinical team diagnosed the patient with calculous cholecystitis; however, surgical intervention was deferred due to significant metabolic instability manifested by hypoglycemia, hypotension, and bradycardia. The patient was subsequently diagnosed with an Addisonian crisis and initiated treatment for adrenal insufficiency. Lab results showed low ACTH (<5.0), FSH (0.90 mIU), LH (0.90 mIU), testosterone (0.01 ng/ml), and prolactin (0.29 ng/ml), indicating hypothyroidism, hypogonadotropic hypogonadism, and leading to a diagnosis of panhypopituitarism.

Contrast-enhanced magnetic resonance imaging (MRI) of the brain (Figure 1) revealed a cystic sellar lesion with no enhancement, exerting compressive effects on the pituitary gland, but without evidence of suprasellar or parasellar extension. The characteristic posterior pituitary bright spot was absent, and a T2 hypointense intracystic nodule was identified. There were no features suggestive of aggressive pathology. Collectively, these findings are consistent with a Rathke cleft cyst resulting in panhypopituitarism.

Figure 1: MRI T2WI sagittal image shows a well-defined intrasellar lesion with a T2 hypointense nodule (A). Sagittal (B) and coronal (C) T1 fat-saturated post-contrast sequences show no evident enhancement of the lesion.

High-resolution scrotal ultrasound (Figure 2) revealed two distinct oval extra-testicular masses in each hemi-scrotum, isoechoic to the testes and sharing the epididymis; one above the right test is, one below the left.

Figure 2: High-resolution ultrasonography of scrotum. Native testes are labeled as ‘Right’ and ‘Left’ in panels A, B, and C. Supernumerary testes appear isoechoic to the native testes and are indicated by stars: on the left side in panels A and B, and on the right side in panel C.

Scrotal MRI showed smaller oval lesions with T2 hyperintensity and T1 isointensity, confirming polyorchidism (Figure 3).

Figure 3: MRI of the scrotum. Native testes are labeled as ‘Right’ and ‘Left’ in panels A, B, and C. Supernumerary testes are visualized as T2 hyperintense extra-testicular nodules in each hemiscrotum, marked with stars in all panels.

Hormone replacement therapy was initiated for panhypopituitarism, with regular monitoring and dose adjustments as indicated. The patient began glucocorticoid replacement using hydrocortisone at a dose of 10 mg in the morning and 5 mg in the afternoon. Levothyroxine 75 mcg once daily was started 48 hours after hydrocortisone initiation.

Urological follow-up of extra testicular tissue for potential malignancy did not identify any complications. Hormone levels, mood, and libido changed following hormone replacement therapy. A 6-month ultrasound indicated stable scrotal findings (Figure 4). The patient attended all scheduled follow-up appointments.

Figure 4: Follow-up ultrasound after 6 months. Native testes are labeled as ‘Right’ and ‘Left’ in panel A. The supernumerary testes remain unchanged and are marked with stars in panels A and B.

Discussion

This report describes a rare clinical case of Rathke's Cleft Cyst found with multiple testes and hormone deficiencies, including panhypopituitarism and other issues affecting the gonads, thyroid, and adrenal glands. These results suggest a potentially intricate association between pituitary development and function, which may be modulated by genetic influences or embryonic disturbances. This underscores its significance as a central topic within the fields of endocrinology and neurology.

Petersson et al analysed the natural history and surgical results of Rathke's cleft cysts using data from the Swedish Pituitary Registry. The study reported that pituitary hormone deficiencies and visual impairments occurred more frequently in cysts larger than 10 mm in diameter. The average cyst diameter at diagnosis was 18 mm (range: 9–30 mm), with 36% of individuals exhibiting pituitary hormone deficiency, 45% showing visual field defects, and 20% experiencing impaired visual acuity. Transsphenoidal surgery was performed in 56 patients. After one year, 60% had no cyst remnants, 50% developed pituitary deficiency, 26% had visual field defects, and 12% had impaired visual acuity. Among twelve patients followed up at 10 years after surgery, eight showed growth in cyst remnants or recurrences. [4]

Hanmayyagari et al described a case of a completely suprasellar RCC in a 4.5-year-old child with hypopituitarism, who presented with bilateral cryptorchidism; RCC exerted pressure on the pituitary, inhibiting the release of FSH, LH, GH, and TSH, which resulted in hypogonadism, hyposomatotropism, and hypothyroidism. In this report, following hCG therapy, the patient's gonads descended into the scrotum. The patient continued long-term follow-up with levothyroxine and growth hormone replacement therapy, as post-surgical reassessment revealed no restoration of pituitary function. [5]

The occurrence of multiple testes and hormonal deficiencies together with a Rathke's cleft cyst (RCC) is considered a potential causal association. Research indicates that deletion of the PROP1 gene in mice results in the formation of Rathke's cleft-like cysts, and hypopituitarism, which presents as hormonal deficiencies and cryptorchidism (undescended testes). This evidence implies that certain genetic or developmental mechanisms affecting the pituitary gland may also influence gonadal development, resulting in these combined conditions. [6]

Elarjani et al reviewed Medline and EMBASE for reports on RCC or pituitary apoplexy, identifying 30 articles with histological diagnoses of RCC apoplexy. Among 29 patients (mean age 36.9; 68% female), 86% had hemorrhagic type. Headache was most frequent (93%), followed by hypogonadism (73%) and hormonal deficits (52%). Neurological improvement occurred in 90%, but 45% needed long-term hormone replacement, mainly thyroid hormone. [7]

The coexistence of both conditions necessitates regular monitoring to assess for progression, recurrence, or malignancy. In this case, a follow-up ultrasound of the testes performed at 6 months demonstrated no significant changes (Figure 4).

In summary, the simultaneous occurrence of RCC-induced panhypopituitarism and polyorchidism is rare and may warrant further study of possible developmental or genetic links, despite their distinct embryological origins.

References

1. Shatri J, Ahmetgjekaj I. Rathke's Cleft Cyst or Pituitary Apoplexy: A Case Report and Literature Review. Open Access Maced J Med Sci. 2018; 6:544-547.
2. Balawender K, Wawrzyniak A, Kobos J, Golberg M, Żytkowski A, Zarzecki M, et al. Polyorchidism: An Up-to-Date Systematic Review. J Clin Med. 2023; 12:649.
3. Nurfajri DH, Pranoto D, Pramod SV, Safriadi F, Hernowo BS. Polyorchidism and testicular malignancy, what can we learn: A case report. Urol Case Rep. 2021;39:101828.
4. Petersson M, Berinder K, Eden Engström B, Tsatsaris E, Ekman B, Wahlberg J, et al. Natural history and surgical outcome of Rathke's cleft cysts-A study from the Swedish Pituitary Registry. Clin Endocrinol (Oxf). 2022;96(1):54-61.
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6. Brinkmeier ML, Bando H, Camarano AC, Fujio S, Yoshimoto K, de Souza FS, Camper SA. Rathke's cleft-like cysts arise from Isl1 deletion in murine pituitary progenitors. J Clin Invest. 2020 Aug 3;130(8):4501-4515.
7. Elarjani T, Alhuthayl MR, Dababo M, Kanaan IN. Rathke cleft cyst apoplexy: Hormonal and clinical presentation. Surg Neurol Int. 2021; 12:504.