Managing a patient with both pituitary hypersecretory and hyposecretory manifestations may be perplexing. We report a 14-year-old female who presented with weight gain, polyuria and polydipsia. Biochemical results were consistent with Cushing disease with central diabetes insipidus. Pituitary magnetic resonance imaging showed right adenoma with stalk thickening. The immunohistochemistry staining of both adenomas was positive for adrenocorticotropic hormone, thyroid stimulating hormone, growth hormone and luteinizing hormone. Postoperatively, the patient developed panhypopituitarism with persistent diabetes insipidus. The coexistence of double adenomas can pose diagnostic and management challenges and is a common cause of surgical failure. Intraoperative evaluation is important in the identification of double or multiple pituitary adenomas in a patient presenting with multiple secretory manifestations.
Pituitary ACTH Hypersecretion ; Cushing disease ; Diabetes Insipidus

A 20-year-old male was referred to the Endocrinology Clinic in view of abnormal thyroid function test result and poor development of secondary sexual characteristics. He was born out of non-consanguineous marriage and had a history of breech delivery at term. He had perinatal complications in the form of delayed cry and lower respiratory tract infection. Developmental delay was also present (delayed motor, speech and social milestones). His scholastic performance was below average and he reported being the shortest child in class from kindergarten.
Hypopituitarism

Sheehan’s syndrome is characterized by hypopituitarism following ischemic necrosis of the pituitary gland caused by postpartum hemorrhage and impaired blood supply to the enlarged pituitary gland during pregnancy. The worldwide prevalence has since decreased due to improvements in obstetric care. Behavioral change is a rare presentation and is often misdiagnosed and managed as psychosis. We report a 42-year-old woman presenting with behavioral changes associated with postpartum failure of lactation and amenorrhea. Hormonal work-up revealed panhypopituitarism; serum cortisol, 98.93 (NV: 138–690 nmol/L); free T4, less than 5.15 (NV: 11.5–23.00 pmol/L); free T3, less than 2.30 (NV: 2.89–4.88 pmol/L); FSH, 3.63 (NV: 30–135 mIU/mL); LH, 3.88 (NV: 13–80 mIU/mL); serum estradiol, 3.89 (NV: 10.41–35.0 pg/mL); IGF-1, 13.13 (NV: 56–194 ng/mL); and serum prolactin, 1.8 (NV: 2.6–24.8 ng/mL). Cranial MRI with contrast revealed an atrophic pituitary gland consistent with Sheehan's syndrome. The symptoms improved substantially upon replacement with steroids and thyroid hormones and she was able to resume her routine activities. The psychiatric features of hypopituitarism can be attributed to a combination of hypothyroidism, hypoglycemia, and hypocortisolism and have been shown to reverse with adequate hormone replacement.
Hypopituitarism ; Psychotic Disorders ; Hypopituitarism

Antineoplastic Agents/therapeutic use* ; Bortezomib/therapeutic use* ; Humans ; Inappropriate ADH Syndrome/chemically induced* ; Multiple Myeloma/drug therapy*

This paper discussed the guiding significance of "disease-syndrome-symptom" mode in FU Qing-zhu's Obstetrics and Gynecology(FU Qing-zhu Nyu Ke) for dealing with ovulation disorder infertility caused by hyperprolactinemia(HPRL). FU Qing-zhu's Obstetrics and Gynecology(FU Qing-zhu Nyu Ke) concentrates on the disease entities, main symptoms, pathogenesis, and syndrome differentiation, based on which the prescriptions are prescribed. This reflects the "disease-syndrome-symptom" mode, with the core lying in the "combination of disease with syndrome". The contained Discussion on Menstruation Regulation(Tiao Jing Pian) and Discussion on Getting Pregnant(Zhong Zi Pian) have important reference significance for later doctors in the diagnosis and treatment of inferti-lity, and many prescriptions are still in use due to good effects. It is believed in traditional Chinese medicine(TCM) that HPRL results from kidney deficiency and liver depression, among which kidney deficiency is the main cause. Liver depression accelerates the onset of HPRL, so the kidney-tonifying and liver-soothing herbs were mainly selected. The "disease-syndrome-symptom" mode in FU Qing-zhu's Obstetrics and Gynecology(FU Qing-zhu Nyu Ke) sheds enlightenment on the diagnosis and treatment of ovulation infertility caused by HPRL, in that it is not confined to disease entity and syndrome type. The integration of "disease-syndrome-symptom" highlights the main complaint of patients and emphasizes the main pathogenesis, thus giving full play to the overall advantage of syndrome differentiation. For multiple diseases in FU Qing-zhu's Obstetrics and Gynecology(FU Qing-zhu Nyu Ke) such as infertility due to liver depression, infertility due to obesity, delayed menstruation, and irregular menstruation, although the typical lactation symptom of HPRL is not mentioned, the medication can still be determined according to the chief complaint, syndrome type, and symptoms and signs, making up for the defects of excessive reliance on serum biochemical indicators in modern Chinese medicine. We should learn its diagnosis and treatment thoughts of paying attention to liver, spleen, kidney, and heart, holism, and strengthening body resistance to eliminate pathogenic factors.
Female ; Gynecology ; Humans ; Hyperprolactinemia/drug therapy* ; Infertility ; Obstetrics ; Ovulation ; Pregnancy

We report a case of a 24-year-old Filipino male who complained of general weakness, polydipsia, weight loss, bitemporal headaches, loss of libido and behavioral changes. Endocrine work-up revealed neurogenic diabetes insipidus and panhypopituitarism. Brain MRI showed multiple intracranial tumors in the left frontal lobe, pineal and suprasellar region with moderate non-communicating hydrocephalus. Intracranial mass biopsy with ventriculo-peritoneal shunting was done. Histopathology of the mass and CSF revealed a germinoma. He underwent chemoradiotherapy while on maintenance hormone replacement.
Neoplasms, Germ Cell and Embryonal ; Germinoma ; Hypopituitarism ; Diabetes Insipidus

Pituitary immune-related adverse events induced by programmed cell death protein 1 inhibitors in advanced lung cancer patients: A report of 3 cases SUMMARY Programmed cell death protein 1 (PD-1) and its ligand 1 (PD-L1) have been widely used in lung cancer treatment, but their immune-related adverse events (irAEs) require intensive attention. Pituitary irAEs, including hypophysitis and hypopituitarism, are commonly induced by cytotoxic T lymphocyte antigen 4 inhibitors, but rarely by PD-1/PD-L1 inhibitors. Isolated adrenocorticotropic hormone(ACTH) deficiency (IAD) is a special subtype of pituitary irAEs, without any other pituitary hormone dysfunction, and with no enlargement of pituitary gland, either. Here, we described three patients with advanced lung cancer who developed IAD and other irAEs, after PD-1 inhibitor treatment. Case 1 was a 68-year-old male diagnosed with metastatic lung adenocarcinoma with high expression of PD-L1. He was treated with pembrolizumab monotherapy, and developed immune-related hepatitis, which was cured by high-dose methylprednisolone [0.5-1.0 mg/(kg·d)]. Eleven months later, the patient was diagnosed with primary gastric adenocarcinoma, and was treated with apatinib, in addition to pembrolizumab. After 17 doses of pembrolizumab, he developed severe nausea and asthenia, when methylprednisolone had been stopped for 10 months. His blood tests showed severe hyponatremia (121 mmol/L, reference 137-147 mmol/L, the same below), low levels of 8:00 a.m. cortisol (< 1 μg/dL, reference 5-25 μg/dL, the same below) and ACTH (2.2 ng/L, reference 7.2-63.3 ng/L, the same below), and normal thyroid function, sex hormone and prolactin. Meanwhile, both his lung cancer and gastric cancer remained under good control. Case 2 was a 66-year-old male with metastatic lung adenocarcinoma, who was treated with a new PD-1 inhibitor, HX008, combined with chemotherapy (clinical trial number: CTR20202387). After 5 months of treatment (7 doses in total), his cancer exhibited partial response, but his nausea and vomiting suddenly exacerbated, with mild dyspnea and weakness in his lower limbs. His blood tests showed mild hyponatremia (135 mmol/L), low levels of 8:00 a.m. cortisol (4.3 μg/dL) and ACTH (1.5 ng/L), and normal thyroid function. His thoracic computed tomography revealed moderate immune-related pneumonitis simultaneously. Case 3 was a 63-year-old male with locally advanced squamous cell carcinoma. He was treated with first-line sintilimab combined with chemotherapy, which resulted in partial response, with mild immune-related rash. His cancer progressed after 5 cycles of treatment, and sintilimab was discontinued. Six months later, he developed asymptomatic hypoadrenocorticism, with low level of cortisol (1.5 μg/dL) at 8:00 a.m. and unresponsive ACTH (8.0 ng/L). After being rechallenged with another PD-1 inhibitor, teslelizumab, combined with chemotherapy, he had pulmonary infection, persistent low-grade fever, moderate asthenia, and severe hyponatremia (116 mmol/L). Meanwhile, his blood levels of 8:00 a.m. cortisol and ACTH were 3.1 μg/dL and 7.2 ng/L, respectively, with normal thyroid function, sex hormone and prolactin. All of the three patients had no headache or visual disturbance. Their pituitary magnetic resonance image showed no pituitary enlargement or stalk thickening, and no dynamic changes. They were all on hormone replacement therapy (HRT) with prednisone (2.5-5.0 mg/d), and resumed the PD-1 inhibitor treatment when symptoms relieved. In particular, Case 2 started with high-dose prednisone [1 mg/(kg·d)] because of simultaneous immune-related pneumonitis, and then tapered it to the HRT dose. His cortisol and ACTH levels returned to and stayed normal. However, the other two patients' hypopituitarism did not recover. In summary, these cases demonstrated that the pituitary irAEs induced by PD-1 inhibitors could present as IAD, with a large time span of onset, non-specific clinical presentation, and different recovery patterns. Clinicians should monitor patients' pituitary hormone regularly, during and at least 6 months after PD-1 inhibitor treatment, especially in patients with good oncological response to the treatment.
Adenocarcinoma of Lung/drug therapy* ; Adrenocorticotropic Hormone/therapeutic use* ; Aged ; B7-H1 Antigen/therapeutic use* ; Humans ; Hydrocortisone/therapeutic use* ; Hyponatremia/drug therapy* ; Hypopituitarism/drug therapy* ; Immune Checkpoint Inhibitors ; Lung Neoplasms/pathology* ; Male ; Methylprednisolone/therapeutic use* ; Middle Aged ; Nausea/drug therapy* ; Pituitary Gland/pathology* ; Pneumonia ; Prednisone/therapeutic use* ; Programmed Cell Death 1 Receptor/therapeutic use* ; Prolactin/therapeutic use*

Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation syndrome (ROHHADS) is a rare multi-system disease, and delayed diagnosis and treatment may lead to catastrophic cardiopulmonary complications. As far as we know, no patient with ROHHADS has been reported in China, and this article reports a child with ROHHADS to improve the awareness of this disease among clinicians. A girl, aged 3 years, had the clinical manifestations of rapid weight gain, fever, disturbance of consciousness, and convulsion. The physical examination showed a body weight of 20 kg, somnolence, irregular breathing, and stiff neck. She had increased blood levels of prolactin and follicle-stimulating hormone and hyponatremia. The lumbar puncture showed an increased intracranial pressure. The brain MRI and magnetic resonance venography showed symmetrical lesions in the periventricular region and venous thrombosis in the right transverse sinus and the superior sagittal sinus. The sleep monitoring showed hypopnea. The girl was finally diagnosed with ROHHADS and intracranial venous thrombosis. She recovered after symptomatic treatment including decreasing intracranial pressure, anticoagulation, and respiratory support. The possibility of ROHHADS should be considered for patients with unexplained obesity, fever, and hypoventilation, with or without central nervous system symptoms. Early diagnosis and standardized follow-up can improve the prognosis of children with ROHHADS.
Child ; Child, Preschool ; China ; Consciousness ; Female ; Humans ; Hypothalamic Diseases ; Hypoventilation ; Obesity

Hyperprolactinemia(HPRL) is one of the diseases leading to anovulatory infertility, which is a refractory gynecological disease and seriously affects female reproductive function. Professor MA Kun has summarized his experience in clinical and scientific studies for many years. And believes that kidney deficiency is the pathogenesis of HPRL and blood stasis is the dominant pathological manifestation of HPRL and can promote the progress of the disease. In view of this, Professor MA Kun took the therapy of kidney-tonifying and blood-activating as the principle for treating anovulatory infertility caused by HPRL, with soothing the liver and promoting Qi as adjuvant therapies. She has also summarized and refined the prescriptions for tonifying kidney and inducing ovulation, which have a remarkable clinical efficacy.
Drugs, Chinese Herbal/therapeutic use* ; Female ; Humans ; Hyperprolactinemia/drug therapy* ; Infertility, Female/etiology* ; Kidney ; Medicine, Chinese Traditional

Pituitary stalk lesions can represent a wide range of pathologies. The exact cause is often unknown due to hesitancy to proceed with biopsy. We present a 16-year-old adolescent who presented with delayed puberty, short stature and bilateral cryptorchidism. He was found to have a thickened pituitary stalk of uncertain etiology with partial hypopituitarism (gonadotrophin and growth hormone deficiency) on further assessment. The presence of bilateral cryptorchidism and micropenis represents lack of “mini puberty,” a phenomenon of activation of the hypothalamic-pituitary-gonadal (HPG) axis in-utero or within the first few months of life.1 These key clinical features have been useful to establish an early temporal relationship and suggest a congenital origin of disease. This enabled a more conservative approach of surveillance to be employed as opposed to invasive pathological examination with pituitary stalk biopsy.
Pituitary Diseases ; Hypopituitarism ; Cryptorchidism ; Growth Hormone