BACKGROUND: Lymphocytic hypophysitis is a rare autoimmune condition that usually presents during pregnancy and causes inflammation of the pituitary gland. Although the pathophysiology is not well understood, it often presents with headaches, visual disturbances, and symptoms of hypopituitarism. However, not all cases may present with hypopituitarism which can make this rare disease with an incidence of ~ 1 in 9 million much more difficult to diagnose.
METHODS: We present a 35-year-old G4P4 woman with progressive vision loss and intermittent frontal headaches during her first trimester through 2 months postpartum. She presented with no symptoms of hypopituitarism and her hormone panel only showed elevated prolactin, possibly due to her breastfeeding. She was treated with a right pterional craniotomy with decompression of both optic nerves, partial resection of the suprasellar mass, and glucocorticoid therapy for headaches and visual disturbances.
CONCLUSIONS: This case is notable for a presentation of lymphocytic hypophysitis without symptoms of hypopituitarism. This is important for outpatient providers to be aware of, especially those that care for pregnant patients so that unfavorable outcomes can be avoided.

Osteogenesis imperfecta (OI) is a rare hereditary bone fragility disorder that affects 6-7 per 100,000 populations, and pituitary stalk interruption syndrome (PSIS) is a rare congenital defect with varying degrees of pituitary hormone deficiency, affecting approximately 0.5 in every 100,000 births. Currently, only two cases of these complications have been reported. A 46-year-old male who had experienced more than 20 fractures (peripheral and vertebral) during adolescence visited our hospital for close examination. He presented with blue sclerae and long bone deformations. We suspected OI because his mother and sister, who were being treated for osteoporosis, also had blue sclerae. Genetic testing identified a heterozygous variant (c.757C > T, p.Arg253Ter) in the COL1A1 gene, leading to the diagnosis of OI. His mother and sister also had the same variant. Considering that he underwent GH replacement therapy for his short stature during his childhood, his pituitary hormone levels were also evaluated to know if GH deficiency impacted low bone density; hypopituitarism was then suspected. The pituitary function test results led to the diagnoses of hypothalamic GH deficiency, hypogonadism, hypothyroidism, and hypoadrenocorticism. Furthermore, magnetic resonance imaging showed anterior pituitary atrophy, pituitary stalk loss, and ectopic posterior pituitary, leading to the diagnosis of PSIS. The combination of OI and hypopituitarism may have caused further bone fragility. Therefore, although rare, clinicians should keep in mind that patients with OI can possibly have concomitant pituitary insufficiency, which can lead to developmental and growth retardation.

In recent years, variants in immunoglobulin superfamily member 1 (IGSF1) have been associated with congenital hypopituitarism. Initially, IGSF1 variants were only reported in patients with central hypothyroidism (CeH) and macroorchidism. Later on, IGSF1 variants were also reported in patients with additional endocrinopathies, sometimes without macroorchidism. We studied IGSF1 as a new candidate gene for patients with combined CeH and growth hormone deficiency (GHD). We screened 80 male and 14 female Dutch patients with combined CeH and GHD for variants in the extracellular region of IGSF1, and we report detailed biomedical and clinical data of index cases and relatives. We identified three variants in our patient cohort, of which two were novel variants of unknown significance (p.L570I and c.1765+37C>A). In conclusion, we screened 94 patients with CeH and GHD and found variants in IGSF1 of which p.L570I could be of functional relevance. We provide detailed phenotypic data of two boys with the p.C947R variant and their large family. The remarkable phenotype of some of the relatives sheds new light on the phenotypic spectrum of IGSF1 variants.

Idiopathic Intracranial Hypertension is a neurological disorder primarily affecting overweight women of childbearing age. It is often characterized by radiologic evidence of empty sella (ES), which is in turn frequently associated with pituitary dysfunction, with the somatotropic axis most commonly affected. No recent evidence is available relative to the presence of pituitary hormone deficiencies in adult patients with Idiopathic Intracranial Hypertension (IIH) under pharmacological therapy. We therefore explored pituitary function and morphology in a small cohort of female patients with IIH treated with acetazolamide. Fifteen female patients aged 42 ± 13 years with IIH lasting between 12 and 18 months were evaluated. All patients were affected by recurrent headaches in addition to visual changes of variable severity. IIH diagnosis was made after exclusion of other causes of raised intracranial pressure, and a specific ophthalmological evaluation was conducted to assess for the presence of papilledema. No particular endocrinological disturbances were detected during the enrolment visits, except for a high obesity prevalence (87%, BMI 35.16 ± 8.21 kg/m2), one case of total thyroidectomy for papillary thyroid carcinoma and two patients with irregular menses and mild hirsutism. All the participants underwent a pituitary MRI with contrast, and two different operators performed pituitary measurements in coronal and sagittal scans for morphologic assessment. Blood samples for the anterior pituitary axis evaluation were collected, and the somatotropic axis was further evaluated with a GHRH + Arginine test; other dynamic tests were performed in case of suspected hormonal deficiency. Despite ES being found in 73% of the patients, pituitary volume was preserved, ranging from 213.85 to 642.27mm3 (389.20 ± 125.53mm3); mean coronal pituitary height was 4.53 ± 1.33 mm. Overall, baseline anterior pituitary hormones levels were within normal ranges, and none of the patients with ES had an altered response to the GHRH + arginine stimulation test. We found one patient suffering from iatrogenic hyperthyroidism and two diagnosed with subclinical primary hypothyroidism due to Hashimoto\'s thyroiditis. Two young patients were suspected of having polycystic ovary syndrome, and they were therefore further investigated. In conclusion, this case series shows that, despite the high prevalence of ES, the pituitary function of IIH patients treated with acetazolamide is preserved. To date, there is no evidence regarding the trend over time or upon treatment discontinuation in regard to the pituitary function of patients with IIH, and it is therefore not possible to infer whether our finding would be replicable in such settings. We therefore suggest an endocrine follow-up over time in order to monitor for potential pituitary dysfunction.

BACKGROUND: Primary Empty Sella (PES) syndrome is an increasingly common disorder, mostly diagnosed as an incidental finding during brain imaging scans. We intended to review the clinical management and hormonal profile of patients with PES.
METHODS: The study included ten-year retrospective analysis of registry containing PES cases in the period 2007 to 2017, from a single tertiary care center. The keyword \'primary empty sella\' was used to retrieve patient details from the radiology unit. The clinical and biochemical profile of PES patients was analyzed. Case management of PES patients and their rate of referral to endocrinologists was explored.
RESULTS: The registry had 765 cases with a male: female ratio of 1:3.8 suggesting female predominance by almost four times. Although not significant, the onset of disease was earlier for males [Mean ± standard deviation (SD) (46.7 years ±17.3 vs 48.8 years±14.1), p = 0.110]. Almost 79% of the cases were found as an incidental finding during Magnetic Resonance Imaging. Of the total PES cases, only 20% were referred to the endocrinologists and the rest were handled by general physicians. Only 1-2.5% of the cases were evaluated for gonadal, growth and adrenal hormones by the general physicians. The hormonal evaluation by the endocrinologists was also found to be sub-optimal. Headache and visual disturbances were the most common presenting complaints followed by menstrual abnormalities. Endocrine abnormalities like thyroid dysfunction, hyperprolactinemia, hypogonadism and hypocortisolism were highly prevalent among those assessed.
CONCLUSIONS: There is a gross under-evaluation of hormonal assessment and minimal case-referral to Endocrinologists. PES is associated with varying degrees of hormonal dysfunction, and hence early assessment and management is needed. Establishing a standard protocol for diagnosis and case management is essential with the involvement of a multidisciplinary team consisting of endocrinologists, neurologists, primary care phys icians and ophthalmologists.

Pycnodysostosis is a rare autosomal recessive osteosclerotic bone disorder associated with short stature and multiple bony abnormalities. Growth hormone (GH) deficiency may contribute to short stature in about 50% of patients. Available literature has rarely reported other pituitary hormone deficiencies in pyknodysostosis. Though the management remains conservative, recombinant human GH (rhGH) has been tried in selected patients. Here we present a case of pycnodysostosis which was evaluated for associated co-morbidities and found to have multiple pituitary hormone deficiencies. A 7-year-old girl was referred to our centre for evaluation of short stature. On examination, she had frontal and occipital bossing, limited mouth opening, hyperdontia with multiple carries, short and stubby digits and short stature. Investigation revealed dense sclerotic bones with frontal and occipital bossing, non-fusion of sutures with obtuse mandibular angle, non-pneumatised sinuses, small ‘J’ shaped sella turcica, acro-osteolysis of digits and absent medullary cavities. Cathepsin-K gene mutation analysis confirmed the diagnosis of pycnodysostosis. She was screened for associated co-morbidities and was found to have concomitant GH deficiency. Treatment with rhGH brought about an increase of 1 standard deviation score in height over 2 years and also unmasked central hypothyroidism at three months necessitating thyroxine replacement.

BACKGROUND: Acromegaly caused by Rathke cleft cyst (RCC) mimicking a plurihormonal pituitary adenoma (PA) is rare.
METHODS: We report a 71-year-old woman who presented with hyperhidrosis in 2013. Magnetic resonance imaging performed in April 2018 revealed that the patient had a pituitary tumor, and she was referred to our hospital. She presented with an acromegaly-like appearance with mild hypertrophy at her limb extremities. Preoperative blood tests, magnetic resonance imaging, and an endocrine tolerance test indicated that the patient\'s symptoms satisfied the diagnostic criteria for acromegaly, with a suspected diagnosis of an RCC and growth hormone (GH)-producing PA. Endoscopic transsphenoidal surgery (eTSS) was performed. Permanent pathologic diagnosis showed an RCC mimicking a plurihormonal PA, which was confirmed via immunohistochemistry. Blood sampling 2 months post surgery showed reduced GH (0.41 ng/mL) and increased insulin-like growth factor-1 (IGF-1) (356 ng/mL) levels. In addition, a postoperative endocrine tolerance test revealed a parasitic reaction of GH and secondary adrenocortical hypofunction. No RCC recurrence was found, and the GH (0.32 ng/mL) and previously increased IGF-1 (169 ng/mL) levels were normalized 12 months after eTSS.
CONCLUSIONS: We reported a rare case of acromegaly caused by RCC mimicking a plurihormonal PA. This case suggests that inflammation associated with RCC might be involved in the development of adenomatous cells. Postoperative clinical symptoms and elevated fibrinogen and IGF-1 levels later improved. This outcome suggested that the transient increase in IGF-1 2 months after surgery might reflect RCC-induced inflammation.

Lymphocytic hypophysitis (LH) is a rare inflammatory disorder involving the pituitary gland, often with other autoimmune diseases combined. The coexistence of LH and Behçet\\\'s disease (BD) is a rare combination and only one case was reported in the previous literatures. A 50-year-old man was admitted into Sir Run Run Shaw Hospital presented with frontal headache and fatigue which had lasted for four months. Endocrinological inspection indicated anterior pituitary dysfunction. Magnetic resonance imaging (MRI) revealed homogeneous pituitary enlargement and thickened pituitary stalk. Administration of glucocorticoids could effectively relieve headache and reduced pituitary mass volume. Oral aphthosis, skin lesions and positive pathergy tests were recognized later, which were characteristic features of BD. Although the diagnosis of BD is mainly dependent on clinical manifestations, PT is still a useful diagnostic tool 0f high specificityfor BD. And this male patient was diagnosed with both LH and BD afterwards. Then he was treated with cyclophosphamide and medium doses of methylprednisolone and remained in good conditions at the follow-up. LH and BD might share a common underlying autoimmune pathogenesis. The presentation of endocrinologic disturbances such as anterior pituitary dysfunction with typical features of skin lesions should prompt further investigation of possible comorbid autoimmune disease involving multiple organ systems. Early diagnosis and close monitoring are vitally important to ensure a stable endocrinologic status.

OBJECTIVE In 2004, the WHO classified atypical pituitary adenoma as a distinct adenoma subtype. However, the clinical significance of this distinction remains undetermined. The authors sought to define patient characteristics, tumor features, and treatment outcomes associated with atypical pituitary adenoma. METHODS The authors reviewed records of patients who underwent resection of pituitary adenoma at the University of California, San Francisco, between 2007 and 2014. Per institutional protocol, adenomas exhibiting mitotic activity underwent evaluation for all 3 markers of atypicality (mitotic index, extensive p53 staining, and MIB-1 index ≥ 3%). Statistical analyses were performed using χ2, Fisher\'s exact test, t-test, log-rank, and logistic regression. RESULTS Between 2007 and 2014, 701 patients underwent resection for pituitary adenoma. Among these patients, 122 adenomas exhibited mitotic activity and therefore were evaluated for all 3 markers of atypicality, with 36 tumors (5%) proving to be atypical. There were 21 female patients (58%) and 15 male patients (42%) in the atypical cohort, and 313 female patients (47%) and 352 male patients (53%) in the nonatypical cohort (p = 0.231). The mean age of patients in the atypical cohort was 37 years (range 10-65 years), which was significantly lower than the mean age of 49 years (range 10-93 years) for patients in the nonatypical cohort (p < 0.001). The most common presenting symptoms for patients with atypical adenomas were headaches (42%) and visual changes (33%). Atypical adenomas were more likely to be functional (78%) than nonatypical adenomas (42%; p < 0.001). Functional atypical adenomas were significantly larger than functional nonatypical adenomas (mean diameter 2.2 vs 1.4 cm; p = 0.009), as were nonfunctional atypical adenomas compared with nonfunctional nonatypical adenomas (mean diameter 3.3 vs 2.3 cm; p = 0.01). Among the entire adenoma cohort, larger presenting tumor size was associated with cavernous sinus invasion (p < 0.001), and subtotal resection was associated with cavernous sinus invasion (p < 0.001) and larger size (p < 0.001) on binomial multivariate regression. The median time until recurrence was 56 months for atypical adenomas, 129 months for functional nonatypical adenomas, and 204 months for nonfunctional nonatypical adenomas (p < 0.001). Functional atypical adenomas recurred more frequently and significantly earlier than functional nonatypical adenomas (p < 0.001). When accounting for extent of resection, cavernous sinus invasion, size, age, sex, and functional subtype, atypicality remained a significant predictor of earlier recurrence among functional adenomas (p = 0.002). CONCLUSIONS When compared with nonatypical pituitary adenomas, atypical adenomas are more likely to present in younger patients at a larger size, are more often hormonally hypersecretory, and are associated with earlier recurrence. These features lend credence to atypical pituitary adenomas being a distinct clinical entity in addition to a discrete pathological diagnosis.

A case-control study was conducted in 2013 to investigate the use of pituitary-derived hormones from sheep as a potential risk factor for the presence of atypical scrapie in Great Britain sheep holdings. One hundred and sixty-five holdings were identified as cases. Two equal sets of controls were selected: no case of scrapie and cases of classical scrapie. A total of 495 holdings were selected for the questionnaire survey, 201 responses were received and 190 (38.3 per cent) were suitable for analysis. The variables \'use-of-heat-synchronisation/superovulation\' and \'flock size\' were significantly associated with the occurrence of atypical scrapie. Farms with atypical cases were less likely (OR 0.25, 95 per cent CI 0.07 to 0.89) to implement heat synchronisation/superovulation in the flock than the control group. Atypical cases were 3.3 times (95 per cent CI 1.38 to 8.13) more likely to occur in large holdings (>879 sheep) than in small flocks (<164 sheep). If the \'use-of-heat-synchronisation/superovulation\' is a proxy for the use of pituitary-derived hormones, the significant negative association between having a case of atypical scrapie and the use of these practices rules out the initial hypothesis that using these drugs is a risk factor for the occurrence of atypical scrapie. Flock size was a significant risk factor for atypical scrapie, consistent with a previous generic case-control study.