Introduction: Pituitary stalk interruption syndrome (PSIS) is a rare congenital disorder characterized by the neuroradiological triad of an absent or interrupted pituitary stalk, ectopic posterior pituitary, and anterior pituitary hypoplasia. It is typically diagnosed in infancy or childhood due to growth failure or delayed puberty. Diagnosis in adulthood is uncommon and may occur after decades of untreated hypopituitarism. Case: A 34-year-old Malay male with underlying physical and intellectual disability presented after a mechanical fall resulting in left slipped capital femoral epiphysis, an unusual pathological fracture in adulthood. Clinical examination revealed marked infantilism with complete absence of secondary sexual characteristics (Tanner stage I). Laboratory evaluation demonstrated combined pituitary hormone deficiency, including severe central hypothyroidism, profound hypogonadotropic hypogonadism, and central adrenal insufficiency. Growth hormone and insulin-like growth factor 1 were undetectable, while prolactin was mildly elevated, consistent with pituitary stalk disruption due to loss of hypothalamic dopaminergic inhibition. Bone age assessment showed severe delay, corresponding to 15 years. Pituitary magnetic resonance imaging demonstrated the classical PSIS triad: anterior pituitary hypoplasia with partial empty sella, a high T1 signal nodule at the median eminence representing ectopic posterior pituitary, and non-visualization of the infundibulum, consistent with an absent pituitary stalk. Birth history revealed premature breech delivery, a recognized perinatal risk factor. The patient was commenced on hormone replacement therapy, including levothyroxine, hydrocortisone, testosterone undecanoate, and calcium–vitamin D supplementation. Conclusion This case illustrates that PSIS may remain undiagnosed into adulthood, leading to severe consequences of long-standing hypopituitarism such as osteoporosis and pathological fractures. Clinicians should consider hypopituitarism in adults presenting with unexplained fractures and delayed sexual maturation, particularly when supported by a suggestive perinatal history.
Fractures, Spontaneous ; Pituitary Gland

Introduction: Langerhans cell histiocytosis (LCH) is a clonal proliferative disorder of langerin-positive histiocytes. Endocrine involvement most frequently manifests as central diabetes insipidus or secondary hypothyroidism, caused by infiltration of the hypothalamic-pituitary axis. Conversely, direct infiltration of the thyroid gland leading to primary hypothyroidism is an exceptionally rare clinical entity, particularly when presenting concurrently with central disease. Case: A 21-year-old female with known right otic and multisystem LCH presented with septic shock secondary to a right ear abscess accompanied by polyuria and polydipsia. Physical examination revealed a palpable goiter. Clinical and biochemical evaluation confirmed central diabetes insipidus with associated anterior hypopituitarism (low adrenocorticotropic hormone, follicle-stimulating hormone, and luteinizing hormone). However, concurrent thyroid function tests demonstrated overt primary hypothyroidism, evidenced by an appropriately elevated thyroid-stimulating hormone (26.19 mIU/L) and low free T4 (5.47 pmol/L), rather than the anticipated secondary hypothyroidism. Neck ultrasound showed diffuse thyroid enlargement with heterogeneous echotexture. Crucially, anti-thyroid peroxidase and anti-thyroglobulin antibodies were both negative, rendering Hashimoto’s thyroiditis highly unlikely. Although the patient declined confirmatory fine-needle aspiration, the constellation of a palpable goiter, characteristic ultrasonographic findings, negative autoimmunity, and active multisystem disease strongly supported a diagnosis of direct histiocytic infiltration of the thyroid gland. She was initiated on appropriate glucocorticoid coverage and subsequent levothyroxine replacement, alongside systemic intravenous cytarabine. Conclusion This case highlights a rare, mixed endocrine profile in multisystem LCH, demonstrating that pituitary and direct end-organ infiltration can coexist. Hypothyroidism in LCH patients with established central diabetes insipidus should not be reflexively assumed to be central in origin. A comprehensive diagnostic workup, including autoantibody screening, ultrasound, and ideally histopathological confirmation, is essential to accurately identify primary endocrine failure and guide appropriate clinical management in these complex cases.
Histiocytosis, Langerhans-Cell ; Hypothyroidism ; Pituitary Gland

OBJECTIVE

This study determined the incidence of perioperative complications associated with routine preoperative glucocorticoid use in patients undergoing pituitary surgery with normal preoperative hypothalamo-pituitary-adrenal axis (HPA axis).

From 2011-2021 retrospective chart review, 243 patients undergoing pituitary surgery with normal preoperative HPA axis were analyzed into 2 groups: 1) with preoperative steroids and 2) without preoperative steroids.  Development of postoperative complications was subsequently evaluated.

Incidence of primary composite postoperative complications of in-hospital mortality, postoperative infection and postoperative diabetes insipidus (DI) was significantly increased among those who had preoperative steroids compared to those without (58.33% versus 33.33%, p-value 0.004)  with an adjusted odds ratio of 2.90 (CI 1.29 to 6.53, p-value 0.010). Among the components of the composite outcome, post-operative DI was statistically higher among those who were given preoperative steroids (52.45% versus 28.21%, p-value 0.006) with an adjusted OR of 3.31 (CI 1.43 to 7.67, p-value 0.005). The incidence of postoperative adrenal insufficiency was similar between the 2 groups (20.15% with steroids versus 8.70% without steroids, p-value 0.258).

Among patients with normal preoperative HPA axis, the routine use of preoperative steroids is associated with an increased risk of composite postoperative complications (in-hospital mortality, postoperative infection and postoperative DI). Steroid-sparing protocol is not associated with an increased risk of postoperative AI. The findings will encourage more rational use of steroids and minimize preventable complications.

OBJECTIVE: To explore the mechanism of acupuncture on improving ovarian hypofunction in aged rats from two perspectives: the overall regulation of the hypothalamic-pituitary-ovarian (HPO) axis and the local ovarian follicle stimulating hormone (FSH)/cyclic adenosine monophosphate (cAMP) signaling pathway. METHODS: Six 3-month-old female SPF-grade Sprague-Dawley (SD) rats were selected as the blank group. Another twelve 9-month-old female SD rats were randomly divided into a model group and an acupuncture group, with six rats in each. The acupuncture group received acupuncture at "Baihui" (GV20), "Guanyuan" (CV4), and bilateral "Ciliao" (BL32) for 20 min per session, once every other day, for a total of 10 sessions. Vaginal smear tests were performed daily to observe the estrous cycle of the rats. Ovarian morphology was observed using HE staining, and follicles at various stages were counted. ELISA was used to detect levels of serum FSH, luteinizing hormone (LH), estradiol (E₂), anti-müllerian hormone (AMH), hypothalamic gonadotropin-releasing hormone (GnRH), pituitary FSH and LH, and ovarian cAMP. Immunohistochemistry and Western blot were used to detect the protein expression of ovarian cAMP protein kinase catalytic subunit, FSH receptor (FSHR), and P450. Real-time quantitative PCR was used to measure mRNA expression levels of FSHR and P450 in ovarian tissue. RESULTS: Compared with the blank group, the model group showed an increased rate of estrous cycle disorder (P<0.01), reduced granulosa cell layers with blurred boundaries and disordered arrangement, decreased numbers of developing follicles at all stages, and increased numbers of atretic follicles (P<0.01); the serum levels of FSH and LH were increased (P<0.01), while E₂ and AMH levels were decreased (P<0.01); the hypothalamic GnRH and pituitary FSH and LH levels were elevated (P<0.01), and ovarian cAMP level was decreased (P<0.01); the positive expression and protein expression of ovarian P450, cAMP protein kinase catalytic subunit, and FSHR were reduced (P<0.01), and ovarian FSHR and P450 mRNA expression was decreased (P<0.01). Compared with the model group, the acupuncture group showed a reduced rate of estrous cycle disorder (P<0.01), clear granulosa cell margins, increased numbers of primordial and secondary follicles, and decreased numbers of atretic follicles (P<0.01); the serum FSH and LH levels were decreased (P<0.01, P<0.05), while E₂ and AMH levels were increased (P<0.05, P<0.01); the hypothalamic GnRH and pituitary FSH and LH levels were decreased (P<0.01, P<0.05), and ovarian cAMP level was increased (P<0.01); the positive expression and protein expression of ovarian P450, cAMP protein kinase catalytic subunit, and FSHR were elevated (P<0.01), and ovarian FSHR and P450 mRNA expression was increased (P<0.01). CONCLUSION Acupuncture could delay ovarian hypofunction in aged rats, possibly through regulating the HPO axis and the FSH/cAMP signaling pathway.
Animals ; Female ; Rats ; Rats, Sprague-Dawley ; Follicle Stimulating Hormone/genetics* ; Acupuncture Therapy ; Ovary/metabolism* ; Signal Transduction ; Humans ; Cyclic AMP/metabolism* ; Hypothalamo-Hypophyseal System/metabolism* ; Aging/metabolism* ; Hypothalamus/metabolism* ; Pituitary Gland/metabolism* ; Gonadotropin-Releasing Hormone/metabolism*

Objective To systematically evaluate the effects of total intravenous anesthesia and inhalational anesthesia on postoperative recovery in patients undergoing transsphenoidal pituitary tumor resection.Methods A comprehensive search was conducted in international biomedical databases including Ovid Medline,Embase,CINAHL(EBSCO),Cochrane Library,and Web of Science,from inception to July 4,2023.Additionally,ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing and completed trials.The randomized controlled trials(RCT)comparing total intravenous anesthesia and inhalational anesthesia in patients undergoing transsphenoidal surgery for pituitary tumors were included.The methodological quality of the included studies was evaluated by the Cochrane Collaboration tool.Relevant data were extracted and synthesized for analysis.Results A total of 327 records were identified,of which eight RCTs met the inclusion criteria.Four studies showed that the patients receiving desflurane or sevoflurane anesthesia experienced faster emergence from anesthesia than those receiving propofol.Two studies indicated that patients in the propofol group had lower levels of emergence agitation and a lower incidence of early postoperative nausea and vomiting.The results on postoperative cognitive function were inconsistent across studies.No differences were found between the groups in terms of postoperative complications or overall recovery quality during hospitalization.Conclusions Inhalational anesthesia appears to provide an advantage in promoting faster emergence following transsphenoidal pituitary surgery,whereas total intravenous anesthesia may contribute to smoother and more stable recovery.Further high-quality studies are needed to clarify the effects of different anesthetic techniques on both short- and long-term postoperative recovery.
Humans ; Anesthesia, Intravenous ; Pituitary Neoplasms/surgery* ; Anesthesia, Inhalation ; Randomized Controlled Trials as Topic ; Anesthesia Recovery Period ; Pituitary Gland/surgery* ; Postoperative Period

OBJECTIVES: To investigate the therapeutic effect of recombinant human growth hormone (rhGH) on children with growth hormone deficiency (GHD) and different pituitary developmental conditions. METHODS: A prospective study was performed on 90 children with GHD who were admitted to Xuchang Maternity and Child Health Hospital from June 2020 to December 2021. According to pituitary height on the median sagittal plane, they were divided into three groups: pituitary dysplasia group (n=45), normal pituitary group (n=31), and enlarged pituitary growth group (n=14). The changes in body height, growth velocity, height standard deviation score and serum levels of insulin-like growth factor binding protein-3 (IGFBP-3) and insulin-like growth factor-1 (IGF-1) were examined after treatment in the above three groups, and the differences of the above indices before and after treatment were compared among the three groups. RESULTS: After treatment, all three groups had significant increases in body height, growth velocity, height standard deviation score, and the serum levels of IGFBP-3 and IGF-1 (P<0.05). Compared with the normal pituitary group, the pituitary dysplasia group and the enlarged pituitary growth group had significantly higher values in terms of the differences in body height, growth velocity, height standard deviation score, IGF-1, and IGFBP-3 before and after treatment (P<0.05). There was no significant difference in the incidence rate of adverse reactions among the three groups (P>0.05). CONCLUSIONS In GHD children with different pituitary developmental conditions, rhGH can promote bone growth and increase body height, especially in children with pituitary dysplasia and pituitary hyperplasia, with good safety.
Child ; Female ; Humans ; Pregnancy ; Body Height ; Human Growth Hormone/therapeutic use* ; Hyperplasia ; Insulin-Like Growth Factor Binding Protein 3 ; Insulin-Like Growth Factor I ; Prospective Studies ; Pituitary Gland/pathology* ; Recombinant Proteins/therapeutic use*

A long-held belief is that pituitary hormones bind to their cognate receptors in classical target glands to actuate their manifold functions. However, a number of studies have shown that multiple types of pituitary hormone receptors are widely expressed in non-classical target organs. Each pituitary gland-derived hormone exhibits a wide range of nonconventional biological effects in these non-classical target organs. Herein, the extra biological functions of pituitary hormones, thyroid-stimulating hormone, follicle-stimulating hormone, luteinizing hormone, adrenocorticotrophic hormone, and prolactin when they act on non-classical organs were summarized, defined by the novel concept of an "atypical pituitary hormone-target tissue axis." This novel proposal explains the pathomechanisms of abnormal glucose and lipid metabolism, obesity, hypertension, fatty liver, and atherosclerosis while offering a more comprehensive and systematic insights into the coordinated regulation of environmental factors, genetic factors, and neuroendocrine hormones on human biological functions. The continued exploration of the physiology of the "atypical pituitary hormone-target tissue axis" could enable the identification of novel therapeutic targets for metabolic diseases.
Humans ; Pituitary Hormones/metabolism* ; Luteinizing Hormone ; Follicle Stimulating Hormone ; Prolactin ; Pituitary Gland/metabolism*

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*

Sleep deprivation (SD) has many deleterious health effects and occurs in more than 70% of pregnant women. However, the changes in sex hormones and relevant mechanisms after SD have not been well clarified. The aim of the present study was to explore the effects of SD on the secretion of sex hormones and the underlying mechanisms. Twelve pregnant Wistar rats were divided into control (CON, n = 6) and SD (n = 6) groups. Pregnant rats in the SD group were deprived of sleep for 18 h, and allowed free rest for 6 h, and then the above procedures were repeated until delivery. The CON group lived in a 12 h light/dark light cycle environment. Estradiol (E2) and progesterone (P4) levels were detected by enzyme-linked immunosorbent assay (ELISA), and the expression of circadian clock genes, Bmal1, Clock and Per2, in hypothalamus and pituitary gland tissues were evaluated by immunohistochemistry (IHC) and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The PI3K and Akt phosphorylation levels in the hypothalamic and pituitary tissues were determined by Western blot. The results showed that, compared with the CON group, the SD group exhibited significantly reduced serum E2 and P4 levels, down-regulated Bmal1, Clock and Per2 expression, as well as decreased phosphorylation levels of PI3K and Akt. But there was no significant difference of the total PI3K and Akt protein expression levels between the two groups. These results suggest that SD might affect the expression of the circadian clock genes in the hypothalamus and pituitary via PI3K/Akt pathway, and subsequently regulate the secretion of sex hormones in the pregnant rats, which hints the important roles of SD-induced changes of serum sex hormone levels in the pregnant rats.
ARNTL Transcription Factors/metabolism* ; Animals ; Circadian Clocks/physiology* ; Circadian Rhythm/genetics* ; Female ; Gene Expression Regulation/genetics* ; Gonadal Steroid Hormones/metabolism* ; Hypothalamus/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Pituitary Gland/metabolism* ; Pregnancy ; Progesterone ; Proto-Oncogene Proteins c-akt/metabolism* ; Rats ; Rats, Wistar ; Signal Transduction ; Sleep Deprivation/metabolism*

Pituitary metastasis,a rare kind of intracranial malignant tumor,is characterized by metastasis from all parts of the body to the pituitary.The common tumors metastatic to pituitary are abundant with blood supply,located in the posterior pituitary lobe and/or the pituitary stalk.The lesion shows infiltrative growth,and mainly demonstrates low signal on T1 weighted imaging and high signal on T2 weighted imaging.It is usually enhanced significantly after iodinated contrast administration.The metastatic tumor with poor blood supply is similar to pituitary macroadenoma on magnetic resonance image,which makes it difficult to be differentiated.We reported two cases of pathologically diagnosed pituitary metastasis with poor blood supply and reviewed related papers,aiming to provide the imaging differentiation points of hypovascular pituitary metastasis.
Contrast Media ; Humans ; Magnetic Resonance Imaging ; Pituitary Diseases ; Pituitary Gland ; Pituitary Neoplasms/diagnostic imaging*