The patient was a 36-year-old woman, married, with no children; having completed a higher education, she is a lawyer by profession. In October 2013, the patient sought psychiatric help in an outpatient clinic due to depressed mood, decreased interest, insomnia, feelings of worthlessness, and significant weight change (-10%). MDD, 296.22 [Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR)] was diagnosed, and the patient received escitalopram 20 mg/d, with no improvement after 5 weeks' treatment. Thus, the treatment changed to paroxetine 60 mg/d and trazodone 150 mg/d, which resulted in a marked improvement within 6 weeks (difficulties in starting activities remained).
In January 2014, the patient was diagnosed with Hashimoto autoimmune thyroiditis. Introduction of levothyroxine 75 mg/d was temporally connected to remission of depressive symptoms. The diagnosis was updated to mood disorder due to hypothyroidism with major depressive-like episode, 293.83 (DSM-IV-TR). In March 2015, psychiatric treatment was concluded.
In May 2015, the patient became pregnant. Ultrasound examination revealed multiple birth defects of the fetus, which led to its death in week 16 of the pregnancy. The patient was hospitalized in the Department of Gynaecology and Obstetrics, where she gave birth to a dead fetus. During the event, she experienced intense fear and helplessness. Following the incident, the patient sought psychiatric help, again due to symptoms she had experienced earlier and which had returned, that is, depressed mood, decreased interest, insomnia, and feelings of worthlessness. Additional symptoms of PTSD, unreported previously, ensued: recurrent distressing dreams of the event, the sensation that the traumatic event was recurring, and the inability to recall an important aspect of the trauma (the patient did not remember a part of her stay at the gynecological ward). Attempts at broaching the subject of losing her child were met with defiance and emotional withdrawal. Her general state was characterized by an increased arousal typical of PTSD cases (irritability, outbursts of anger, difficulty concentrating, hypervigilance). The patient no longer managed to function normally in social contexts (workplace, home). MDD, 296.22, was diagnosed with the co-occurrence of acute PTSD, 309.81. Given that selective serotonin reuptake inhibitor (SSRI) medications such as sertraline and paroxetine are approved by the FDA for the treatment of PTSD and with her previous treatment response, we decided to start with paroxetine 20 mg/d and trazodone 75 mg/d. However, no marked improvement was noted following 5 weeks of treatment. Paroxetine was increased up to 60 mg/d and trazodone up to 150 mg/d, the same dose prescribed previously, which has resulted in marked improvement of her MDD.
Due to a massive sleep dysfunction consisting in troubles with falling asleep, frequent waking periods during the night, and a very high level of irritability, as well as multiple outbursts of anger and anxiety, it was necessary to increase the trazodone dose to 200 mg/d and to introduce diazepam in the dose of 5 mg/tds. Moreover, the patient's somatic health condition was deteriorating rapidly. The patient lost weight [-10% within a month; body mass index (BMI) = 19 kg/m2]; she complained of general weakness, dizziness and fainting, as well as of episodes of hyperventilation and paresthesia. Physical examination revealed dehydration and low blood pressure (100/60 mmHg), which plummeted even further when standing (orthostatic hypotension). Assessments of both morning adrenocorticotropin (ACTH) and morning cortisol levels in the blood performed on an outpatient basis revealed slightly decreased results (ACTH = 6.00 pg/ml; cortisol = 4.90 ng/ml). Therefore, in April 2016, the patient was admitted to the Department of Endocrinology with suspicion of adrenal insufficiency.
During the patient's stay at the ward, examination revealed correct circadian rhythm in serum cortisol (6:00, 5.60 mug/dl; 8:00, 11.30 mug/dl; 20:00, 4.40 mug/dl; 24:00, 4.20 mug/dl), as well as correct levels of the hormone in a 24-h sample of urine: 28.2 mug/24. Also, the ACTH concentration in the daily profile of the serum was correct (6:00, 6.12 pg/ml; 8:00, 10.20 pg/ml; 20:00, <5.40 pg/ml; 24:00, 7.07 pg/ml). Thyrotropin concentration (TSH) with both free thyroxine (fT4) and free triiodothyronine (fT3) were within normal range, with elevated anti-thyroid peroxidase (TPO) antibodies, 253 IU/ml (reference range < 35 IU/ml).
In order to assess the ACTH/cortisol axis for detecting secondary adrenal insufficiency, a standard ITT was performed. Symptomatic hypoglycemia, with blood glucose values below 40 mg/dl, was required to evoke a reliable central stress response with the activation of the hypothalamic-pituitary-adrenal (HPA) axis. Intravenous insulin was administered (0.1 units/kg; 6j aspart insulin). Symptomatic hypoglycemia, with blood glucose values of 29 mg/dl within 30 min of the test, was achieved. The patient experienced mild palpitations, massive hot flushes, and sweating, which disappeared within several minutes of the procedure. The results of the test excluded any abnormalities of the ACTH/cortisol and growth hormone secretion ( Table 1 ).
Four days after hospitalization, the patient had a consultation with her psychiatrist (the first author of this manuscript). During the examination, a marked improvement of the patient's mental state was noted. Symptoms of PTSD were reduced: increased arousal diminished, sleep was normalized, and bouts of anxiety became much less frequent and less severe. The patient was able to recall an important aspect of the trauma, and recurrent distressing dreams of the event disappeared. MDD symptoms persisted in the clinical picture, including depressed mood, decreased interest, and feelings of worthlessness. Such results enabled the psychiatrist to take the patient off diazepam (in the course of 10 days).
Over the following month, MDD symptoms gradually became less intense; consequently, trazodone was reduced from 200 to 100 mg/d, and paroxetine from 60 to 40 mg/d. In July 2017, 14 months after the ITT, pharmacological treatment was concluded, and presently, the patient remains in remission and is planning a pregnancy.