Empty sella and periodic mental symptoms: A report of two cases

To the Editor

Empty sella (ES) describes the sella being filled with cerebrospinal fluid and atrophy of the pituitary tissue. Common symptoms include endocrine dysfunction and hypopituitarism, as well as headaches, epilepsy, dizziness, and runny nose (Debnath et al., 2016). Furthermore, psychosis is more likely to occur in ES patients (4.6%) than in the general population (1.3%) (Debnath et al., 2016). We describe two cases provide evidence for investigating the relationship between ES and mental disorders. We have received permission to publish the cases from the participants.

Case 1

A 48-year-old female had shown periodic mental symptoms since the age of 22. The frequency of her symptoms ranged from up to five times a year to once every 2 years. When symptom free, she maintained a normal life. However, she tended to be easily affected by life events.

Her mental symptoms were regular: being talkative and talked to the TV during the first 3 days of each episode; logic barriers and purposeless behaviors from the 4th day to the 20th day, regaining normality between days 25 and 28.

For many years, her daughter secretly administered drugs such as risperidone, haloperidol, clozapine, perphenazine, sulpiride and penfluridol, irregularly through her diet. None could shorten the course of the episodes. No drug side effects were observed until the end of the cycle.

Our team observed two episodes in the patient during hospitalization, each lasting over 20 days. The patient had been treated with haloperidol, sodium valproate, clozapine and quetiapine, but none changed the course of the disease. Laboratory examination results are shown in Table 1. Magnetic resonance imaging (MRI) showed ES (Figure 1(A)).

Figure 1.

Brain imaging of the two cases. (A) SIEMENS Prisma 3.0T magnetic resonance imaging of the brain of Case 1. Empty sella (arrow) was observed. (B) Computed tomography of the brain of Case 2 by GE LightSpeed VCT 64 CT Scanner. Empty sella (arrow) was observed. Because of an indwelling cerebrospinal fluid drainage device, she could not undergo an MRI.

Table 1.

Summary of laboratory investigations of the cases.

Investigation	Result		Reference range
	Case 1	Case 2
Hemoglobin (g/L)	141	148	115–150
Thyroid-stimulating hormone (mIU/L)	2.46	4.48	0.49–4.91
Serum total T3 (nmol/L)	1.29	1.74	1.01–2.48
Free T3 (pmol/L)	5.07	4.36	3.28–6.47
Serum total T4 (nmol/L)	119.35	143.35	69.97–152.52
Free T4 (pmol/L)	11.55	9.63	7.64–16.03
Insulin (pmol/L)	73	61.48	13.00–161.00
Prolactin (mIU/L)	501.8	195.63	70.80–566.20
Estradiol (pmol/L)	110	129	Menopause(0–92.117) Luteal phase(111.3478–1006.4608) Follicular phase(55.6372–543.6371) Ovulation(107.97–1624.4154)
Serum creatinine (μmol/L)	57.1	69	45.0–110.0
Calcium (mmol/L)	2.57	2.38	2.10–2.80
Phosphorus (mmol/L)	1.58	1.38	0.80–1.60
Creatine phosphokinase (U/L)	35	79	25–200
Potassium (mmol/L)	3.59	3.88	3.50–5.30
Sodium (mmol/L)	141.8	143.2	137.0–147.0
Chlorine (mmol/L)	103	103	99.0–110.0

Case 2

A 37-year-old female who underwent two operations for unexplained hydrocephalus in 2014 and 2019 developed extreme sensitivity to inconveniences of daily life after the second operation, leading to symptoms occurred with obvious regularity—for ~40 days each time. At onset, it manifested as unstable walking, trembling, irritability, depression, anxiety and circumstantiality. She was previously treated with sertraline, olanzapine, buspirone and trihexyphenidyl hydrochloride, all with poor effect.

During hospitalization she was treated with escitalopram oxalate. On the 40th day of the episode, her mental symptoms were relieved. Subsequent dysuria was relieved after reducing medication. Laboratory results are shown in Table 1. A brain computed tomography examination showed ES (Figure 1(B)).

Discussion

Except for hyperprolactinemia caused by haloperidol in case 1, both patients had no other obvious symptoms of ES.

There are few reports of ES causing mental symptoms. One study reported that hyponatremia caused by abnormal secretion of the antidiuretic hormone in patients with ES can cause mania (Yang et al., 2016). Schizophrenia-like manifestations caused by Sheehan’s syndrome have also been reported among patients with ES (de Silva et al., 2020).

The current cases had neither hyponatremia nor Sheehan’s syndrome. All characteristics were different, except for their sex and ES. However, their clinical symptoms showed striking similarities, especially the episodic anomalies with clear regularity and predictability. Another similarity was their vulnerability to daily stress and circumstantiality at the onset, which are common features of mental symptoms in patients with organic encephalopathy. The third commonality was the poor response to various drug treatments and that their drug tolerance fluctuated. Therefore, it is reasonable to hypothesize that ES may be related to these periodic mental symptoms or that ES and mental symptoms are both part of some complex disease, such as undetected pituitary dysfunction. To our knowledge, such cases have not been reported, but we believe similar situations exist. Clinicians should perform head MRI examinations when encountering patients with periodic mental symptoms.