Most cases of hypopituitarism arise from destructive processes directly involving the anterior pituitary, including tumors, traumatic brain injury, Sheehan syndrome, apoplexy, inflammatory disorders, and radiation . Brain injury resulting from traumatic thoracic injury , autoimmune disease , and metastasis to the pituitary  are additional reported causes of hypopituitarism. Recently, immune checkpoint inhibitors have been used to treat various types of cancer. With increased use of these inhibitors, physicians should be aware of the possibility of immune checkpoint inhibitor-induced hypophysitis. Cytotoxic T-lymphocyte antigen (CTLA)-4 is expressed in the pituitary gland; anti-CTLA-4 antibodies were reported to induce hypophysitis . Furthermore, anti-programmed cell death (PD)-1 and anti-PD-ligand 1 antibodies have been reported to induce hypophysitis, leading to pituitary atrophy . Therefore, we must be aware of various signs of hypopituitarism when we perform invasive dental treatment.
The anterior lobe of the pituitary has high functional reserve; therefore, more than 75% of the parenchyma must be lost before symptoms of hypopituitarism are seen . In the present case, anterior lobe hormone-stimulation tests revealed hyporeactivity of ACTH, TSH, LH, FSH, prolactin and GH. MRI revealed pituitary atrophy. These results and the medical history of loss of consciousness indicate that the patient’s hypopituitarism might have been gradually progressive before dental treatment. The invasive dental treatment might have decreased the functional reserve of the pituitary, resulting in clinical symptoms.
It is rare that an invasive medical procedure results in diagnosis of hypopituitarism. To the best of our knowledge, two such cases have been reported in the Japanese literature [9, 10]. In these cases, food intake decreased as a result of invasive medical procedures, and the stress of hospitalization increased the relative cortisol requirement. These factors caused adrenal insufficiency to become evident. Hypopituitarism with resulting adrenal insufficiency causes malaise, fatigue, nausea, vomiting, weight loss, and muscle weakness. Adrenal crisis is biochemically characterized by hyponatremia and hypoglycemia in patients with hypopituitarism. Hyperkalemia is not present in hypopituitary patients because they do not have mineralocorticoid deficiency, unlike patients with primary adrenal insufficiency . Surgical stress can result in an adrenal crisis, with shock or disturbed consciousness as symptoms. These symptoms are life-threatening; therefore, urgent administration of hydrocortisone is required . In the present case, the patient’s food intake decreased after invasive dental treatment, resulting in worsening hyponatremia. We attributed the patient’s symptoms to severe pain after dental treatment; however, these symptoms were caused by hypopituitarism with adrenal insufficiency.
Treatment of hypopituitarism is classified as causal or symptomatic. In the present case, neither pituitary surgery nor radiation had been performed, and the cause of hypopituitarism was not obvious; therefore, symptomatic treatment was selected. Because hypopituitarism was diagnosed before the treatment of tongue cancer, adequate perioperative hydrocortisone supplementation was administered. As a result, adrenal crisis was avoided during surgery for tongue cancer.
In conclusion, when decreased appetite, malaise, and fatigue occur after invasive treatments, the possibility of masked hypopituitarism should be considered.