An interesting case of Rathke's cleft cyst presenting as bilateral cryptorchidism.

Rathke's cleft cyst (RCC) are benign, epithelium-lined sellar and suprasellar cysts believed to originate from remnants of the Rathke pouch. Here, we report a rare case of entirely suprasellar RCC in a 4.5-year-old child causing hypopituitarism, who presented to us with bilateral cryptorchidism. Subsequently we discuss the distinct rarity of entirely suprasellar RCC presenting in this fashion and the relevant literature is also discussed.

Introduction

Cryptorchidism, defined as the absence of at least one testis in the scrotum,[1] is a frequent condition in the pediatric population. It affects up to 9% of full-term newborns and up to 1.5% of 1-year-old boys.[2] The most common location for an undescended testicle is just outside the external ring (suprascrotal), followed by the inguinal canal followed by the abdomen.[3] Cryptorchidism occurs more commonly among patients with congenital disorders of testosterone secretion or action, secondary hypogonadism, testosterone biosynthetic defects, or insensitivity syndromes, abdominal wall defects, neural tube defects, cerebral palsy,[4] and various genetic syndromes[5] (e.g., trisomy 18, trisomy 13, Noonan syndrome, Prader-Willi syndrome, and Laurence-Moon-Biedl syndrome).

Rathke cleft cysts (RCCs) are benign, epithelium-lined sellar and suprasellar cysts believed to originate from remnants of the Rathke pouch[6] lying between the pars anterior and the pars intermedia of the pituitary gland. RCCs commonly have a round, ovoid, or dumbbell shape. They are usually asymptomatic and are discovered incidentally, when radiographic or necropsy findings are reviewed. Most cysts are smaller than 2 cm in diameter. Symptomatic RCCs are uncommon, but cysts can enlarge and cause symptoms secondary to compression of the pituitary gland, pituitary stalk, optic chiasm, or hypothalamus. Atypical presentations for RCC include abscess formation within the cyst, aseptic meningitis or entirely suprasellar RCC.[78] The differential diagnoses are cystic craniopharyngioma, arachnoid cyst, and cystic pitutary adenomas. Distinction among these remains a difficult preoperative problem, because the symptoms, signs, and biochemical and radiographic features of these lesions can mimic each other.

Here, we report a rare case of entirely suprasellar Rathke's cleft cyst (RCC) in a 4.5-year old child causing hypopituitarism, who presented to us with bilateral cryptorchidism. Although till date, a few cases of symptomatic RCCs have been reported in world literature, the condition continues to remain largely unknown to practicing clinicians. The current report intends to draw attention towards hypopituitarism as one of the etiology of cryptorchidism. To the best of our knowledge, this is the first case of entirely suprasellar RCC presenting in a child with cryptorchidism to be reported from world literature.

Case Report

A 4.5-year-old boy presented to the Pediatric Surgery Department with bilateral undescended testes for which surgery was planned. Upon evaluation for short stature at the department of endocrinology, he was found to be born to nonconsanguineous parents, at full term by normal vaginal delivery; there was no history of prolonged labor or birth asphyxia and his birth weight was 2.5 kg. Mother noticed bilateral undescended testes at the time of delivery, but was reassured by the doctor that testes would descend subsequently. There was no history of seizures or prolonged jaundice in the neonatal period, but his motor and mental milestones were delayed. He remained shorter than his peers and his sister who is 2 years younger is taller than him. There was no history of chronic systemic disease, hypothyroidism, or features suggestive of raised intracranial pressure. On examination, his height is 84 cm (<3rd percentile), upper to lower segment ratio is 0.9 [Figure 1], standard deviation score was 4, weight was 13 kg, and head circumference was 51 cm. He had frontal bossing, doll-like facies, central obesity, micropenis with stretched penile length of 2 cm, and both gonads were palpable in suprascrotal area with a poorly developed empty scrotal sac. His vitals and systemic examination were normal.

Figure 1

Showing child with short stature, central obesity, micro penis.

Investigations revealed a hemoglobin of 13.6 g% (11-15), total lymphocyte count of 5,600/mm3 (4-11,000), erythrocyte sedimentation rate of 15 (5-20), random blood sugar of 94 mg% (90-130), creatinine 0.8 mg/dl (0.6-1.5), free thyroxine (T4)-0.9 ng/ml (0.93-1.7), thyroid stimulating hormone (TSH)-7.27 mIU/ml (0.3-5.5), bone age-1 year, basal cortisol-13.76 μg/dl (8-20), follicle stimulating hormone (FSH)-0.63 mIU/dl (1.5-10.2), luteinizing hormone (LH)-0.1 mIU/dl (1.9-12), testosterone basal 0.025 ng/ml (3-6.5), stimulated testosterone with human chorionic gonadotropin (hCG) was 0.68 ng/ml (suggestive of normally functioning testes), and insulin-like growth factor 1 (IGF-1) was undetectable. Radiological evaluation revealed bilateral suprascrotal testes in ultrasound abdomen, a 3.8 × 3.6 cm suprasellar cystic lesion with compressed pituitary gland in magnetic resonance imaging (MRI) brain [Figures 2 and 3], which was hypointense on T1 and hyperintense on T2 images suggestive of cystic craniopharyngioma or Rathke's cyst. Child did not cooperate for an accurate visual field examination, but grossly he had some degree of visual impairment in left eye. Urine output and fluid input both were approximately 1 l.

Figure 2

Magnetic resonance imaging (MRI) sagittal section is showing suprasellar Rathke's cleft cyst (RCC) with normal compressed pituitary

Figure 3

MRI coronal section is showing suprasellar RCC

Child was subsequently treated with levothyroxine replacement in view of secondary hypothyroidism. After 4 weeks (with the normalization of T4 levels), he underwent right frontotemporal orbitozygomatic craniotomy, marsupialization of suprasellar cyst along with biopsy. His intra- and postoperative period was uneventful. Biopsy revealed a single-cell layered, cuboidal epithelium, suggesting a Rathke's cleft cyst. So the final diagnosis was Rathke's cleft cyst with hypopituitarism. At 6 and 12 weeks after surgery, child was reevaluated for pituitary function, which revealed persistent secondary hypothyroidism and low IGF-1 levels suggestive of growth hormone deficiency. Levothyroxine was reinstituted followed by initiation of growth hormone replacement along with 5 week hCG therapy (intramuscular (IM) 1,000 IU twice a week). This enabled gonadal descent into the scrotum 3 months after the completion of therapy.

Discussion

RCCs are usually located in an intrasellar or combined intra- and suprasellar location, between the pars anterior and the pars intermedia of the pituitary gland; they are assumed to be benign remnants of the craniopharyngeal duct, which is part of Rathke's pouch. The pars tuberalis of the pituitary gland which lies above the diaphragma sellae, is also derived from Rathke's pouch, and is the site of origin of entirely suprasellar RCCs.[910] But purely suprasellar RCC are distinctly uncommon in clinical practice.

Majority of the RCC are asymptomatic. If the normal involution of Rathke's pouch fails to occur, the resulting RCC may increase in size by accumulation of cyst fluid and compress the surrounding structures with ensuing headache, visual problems, and hypopituitarism.[1112] Entirely suprasellar symptomatic RCCs with normal sella turcica are exceptionally rare and very few case reports are available in world literature.[1013] Further, RCC presenting at such a young age with hypopituitarism has not been reported till date.

Testicular descent occurs in two phases, comprising of transabdominal and inguinoscrotal descent, which occur approximately during the first and last thirds of gestation, respectively. Key anatomical events to release the testis from its urogenital ridge location and to guide the free gonad into the scrotum are the degeneration of the craniosuspensory ligament and a thickening of the gubernaculum. Androgens play a role in both these processes, particularly with respect to enabling the testis to traverse the inguinal canal in the final phase of descent. Androgen induces regression of the craniosuspensory ligament to release the testis to descend. Otherwise, androgens are not required for the first phase of testis descent. The thickening of the gubernaculum, a process crucial for anchoring the testis to the inguinal region is controlled by insulin-like 3 peptide (INSL3) and its G protein coupled receptor (GREAT).[14] In turn, this INSL3 is controlled by hCG and LH.[15]

Even though surgical management is the cornerstone of treatment for cryptorchidism, medical treatment can be effective in the above mentioned endocrine disorders and it is prudent to give a trial before resorting to orchiopexy. Available agents are gonadotropin releasing hormone (GnRH) or hCG injections that produce a significant rise in local testosterone levels;[16] thereby facilitating testicular descent. Commonly used agent is hCG and there are many protocols for the use of hCG.[161718] One such protocol is the administration of 1,000-2,500 IU two times per week intramuscularly for 4-5 weeks. Whatever protocol is used, the likelihood of success is greatest in the most distal true undescended testicles. Complete success was defined as full descent of the testicle into the scrotum and needs assessment between 8 weeks and 6 months after the completion of treatment. These studies have reported temporary virilizing side effects, including increased penile length, erections, and testicular enlargement associated with hormonal treatment. All side effects were transitory.

In the present case, RCC causing a pressure effect on pituitary with subsequent inhibitory effect on the release of FSH, LH, growth hormone (GH), and TSH led to the hypogonadism (perhaps, the RCC was causing this pressure effect from the intrauterine period itself and hence resulted in cryptorchidism) along with hyposomatotropism and hypothyroidism. We also propose that because of its chronic compressive effect with consequent ischemic and pressure necrosis, all cell lineages were affected irreversibly as evidenced by no recovery of pituitary function in the post-surgical reevaluation. After hCG therapy, gonads descended into the scrotum and the patient is on long-term follow-up with replacement of levothyroxine and growth hormone.

Conclusion

In conclusion, RCCs are usually intrasellar or combined intra- and suprasellar, can rarely occur in an entirely suprasellar location with intact diaphragm and intact sella turcica, but a presentation as in our case, with features of hypopituitarism at such a young age, is distinctly uncommon. In the evaluation of cryptorchidism one should explore the possibility of central causes in the etiology, as this may respond to medical therapy, thereby obviating the need for unnecessary surgical intervention.