Pituitary

Multiple posttranslational processes modify native PRL and result in the secretion of several PRL isoforms with different bioactivity. Since we observed that serum samples contain non-lactogenic substances able to interfere in Nb2 cell bioassay, in this study we extracted PRL molecules from sera of pregnant and non-pregnant normal adults, fetuses and patients with prolactinoma and evaluated the ability of partially purified PRL to stimulate Nb2 cell proliferation. The preliminary immunopurification of PRL samples, conferred good sensitivity and specificity to PRL biological assay. Whenever possible, bioactivity values were correlated with glycosylated-PRL levels (G-PRL), the major posttranslational modification known to reduce PRL bioactivity. The ratio of bioactive (B-) vs immunoreactive PRL (I-PRL) (B/I) in normal subjects was 0.9 ± 0.1 (mean±SD), and not affected by TRH and sulpiride administration. PRL B/I ratio did not change during pregnancy, both in maternal (0.8 ± 0.1) and fetal circulation (1.0 ± 0.01). In patients with prolactinoma PRL B/I ratios (0.8 ± 0.18) were in the normal range. However, in 2 women with microprolactinoma, with a clear discrepancy between high I-PRL levels and mild clinical features, a significantly reduced PRL B/I ratio was observed (0.51 ± 0.08 and 0.52 ± 0.1 respectively). Conversely, a woman with clear clinical features of hyperprolactinemia, but border-line elevated I-PRL levels had a PRL B/I ratio in the upper limit of normal range. No variation in G-PRL vs NG-PRL percentages was observed in all the cases studied. In conclusion, our data show that physiological and pathological conditions of hyperprolactinemia, including fetal life, are associated in the majority of cases, with the secretion of PRL molecules with unchanged mitogenic activity on Nb2 cells. Nb2 PRL bioassay may be an useful tool to explain the discrepancies between clinical features and immunoreactive PRL levels in some particular cases.

To understand the natural history and optimal treatment strategy for pituitary gland metastasis. We performed both a retrospective chart review of patients treated at our institution and a scoping review of the topic. The retrospective review identified seven patients with an average age of 59.6 years. Primary histologies included breast cancer (4), melanoma (1), renal cell carcinoma (1), and sarcoma (1). Two patients had anterior pituitary endocrine dysfunction, one of whom was the only patient with visual symptoms. All patients were treated with radiosurgery and two also underwent surgical resection. Overall survival ranged from 6.5 to 117 months. Literature review identified 166 patients from 71 studies. The most common primary cancer was lung (27.7%), followed by breast (18.7%) and renal (14.5%) cancer. 107 presented with endocrine dysfunction, including 41 cases of diabetes insipidus and 55 cases of hypopituitarism. 110 presented with visual compromise. 107 patients received radiotherapy, 96 underwent surgical resection and 44 received systemic chemotherapy/immunotherapy. Surgery was significantly associated with an increased likelihood of vision improvement and a decreased likelihood of endocrine normalization. Radiographic regression predicted visual improvement. Median overall survival was 9.9 months (range: 0.2–96). This scoping review showed that both radiosurgery and surgical resection have been frequently used to treat pituitary metastases with good response. Vision improvement is more likely to happen following surgical resection, likely at the expense of endocrine dysfunction. Despite treatment and radiographic response, patient survival remains less than a year.

The aim of this study was to assess the effects of replacement with recombinant human growth hormone (rhGH) in patients with GH deficiency (GHD) after treatment of acromegaly. Intervention study. Sixteen patients (8 men, age 56 years), treated for acromegaly by surgery and radiotherapy, with an insufficient GH response to insulin-induced hypoglycaemia, were treated with 1 year of rhGH replacement. Study parameters were assessed at baseline and after 1 year of rhGH replacement. Study parameters were cardiac function, body composition, bone mineral density (BMD), fasting lipids, glucose, bone turnover markers, and Quality of Life (QoL). During rhGH replacement IGF-I concentrations increased from −0.4 ± 0.7 to 1.0 ± 1.5 SD (P = 0.001), with a mean daily dose of 0.2 ± 0.1 mg in men and 0.3 ± 0.2 mg in women. Nonetheless, rhGH replacement did not alter cardiac function, lipid and glucose concentrations, body composition or QoL. Bone turnover markers (PINP and β crosslaps) levels increased (P = 0.005 and P = 0.021, respectively), paralleled by a small, but significant decrease in BMD of the hip. The beneficial effects of rhGH replacement in patients with GHD during cure from acromegaly are limited in this study.

Urinary free cortisol (UFC) determination by highly specific methods as mass spectrometry instead of commercially available antibody-based immunoassays is increasingly recommended. However, clinical comparisons of both analytical approaches in the screening of Cushing’s syndrome (CS) are not available. The aim of this study was to evaluate the diagnostic value of mass spectrometry versus immunoassay measurements of 24 h-UFC in the screening of CS. Cross-sectional study of 33 histologically confirmed CS patients: 25 Cushing’s disease, 5 adrenal CS and 3 ectopic CS; 92 non-CS patients; and 35 healthy controls. UFC by immunoassay (UFCxIA) and mass spectrometry (UFCxMS), urinary free cortisone (UFCo) and UFC:UFCo ratio were measured, together with creatinine-corrected values. Sensitivity, specificity, AUC and Landis and Koch concordance index were determined. AUC for UFCxIA and UFCxMS were 0.77 (CI 0.68–0.87) and 0.77 (CI 0.67–0.87) respectively, with a kappa coefficient 0.60 and strong Landis and Koch concordance index. The best calculated cutoff values were 359 nmol/24 h for UFCxIA (78 % sensitivity, 62 % specificity) and 258.1 nmol/24 h for UCFxMS (53 % sensitivity, 86 % specificity). The upper limit of UFCxIA and UCFxMS reference ranges were 344.7 and 169.5 nmol/24 h respectively. Sensitivity and specificity for CS diagnosis at these cutpoints were 84 and 56 % for UFCxIA and 81 and 54 % for UFCxMS. According to our data, both methods present a very similar diagnostic value. However, results suggest that lower cutoff points for mass spectrometry may be necessary in order to improve clinical sensitivity.

Objective Lymphocytic hypophysitis (LH) is a rare chronic inflammatory disorder characterized by lymphocytic infiltration of the pituitary gland commonly affecting women during pregnancy or post-partum period. The pathogenesis remains uncertain, however an autoimmune process is frequently implicated. There is limited data on the occurrence of LH outside the setting of autoimmunity. Case We describe a 37-year-old man presenting with diarrhoea, nausea, weight loss, low-grade fever, headache and cerebrospinal fluid analysis consistent with aseptic meningitis. Magnetic resonance imaging (MRI) demonstrated a homogenously enlarged pituitary gland with biochemical testing revealing partial hypopituitarism with adenocorticotrophic hormone and gonadotrophin deficiency. Notably, his free thyroid hormone levels were elevated with a suppressed thyroid-stimulating hormone and a suppressed thyroid technetium scan consistent with thyroiditis. Tissue antibodies including thyroid antibodies were negative. Following introduction of hydrocortisone, he developed transient diabetes insipidus which spontaneously resolved after 4 months. Thyrotoxicosis resolved after 5 weeks and thyroxine was commenced as he developed secondary hypothyroidism. Repeat MRI 3 months later showed a reduction in the size of the pituitary gland which by 6 months had returned to normal size. He remains well on hydrocortisone, thyroxine and testosterone replacement. Conclusions Based on clinical and radiological grounds, the diagnosis was consistent with lymphocytic hypophysitis associated with subacute thyroiditis. This is only the second report of this combination in the absence of autoimmunity and the first report of LH and thyroiditis with associated aseptic meningitis in the absence of tissue autoantibodies. We propose a possible viral illness as the unifying aetiological cause

Our aim was to investigate the changes in the composition of oral and gut microbiota in patients with newly diagnosed acromegaly and their relationship with IGF-1 levels. Oral and fecal samples were collected from patients with newly diagnosed acromegaly without comorbidities and from healthy controls. The composition of the microbiota was analyzed. The general characteristics, oral and stool samples of the patients and healthy control subjects were compared. The changes in microbiota composition in both habitats, their correlations and associations with IGF-1 were statistically observed using machine learning models. Fifteen patients with newly diagnosed acromegaly without comorbidities and 15 healthy controls were included in the study. There was good agreement between fecal and oral microbiota in patients with acromegaly (p = 0.03). Oral microbiota diversity was significantly increased in patients with acromegaly (p < 0.01). In the fecal microbiota, the Firmicutes/Bacteroidetes ratio was lower in patients with acromegaly than in healthy controls (p = 0.011). Application of the transfer learned model to the pattern of microbiota allowed us to identify the patients with acromegaly with perfect accuracy. Patients with acromegaly have their own oral and gut microbiota even if they do not have acromegaly-related complications. Moreover, the excess IGF-1 levels could be correctly predicted based on the pattern of the microbiome.

We present a patient with a Rathke’s cleft cyst who presented with rapidly progressive bilateral 6th nerve palsy. A 20-year-old woman with a history of cleft palate, hypertension, and hydronephrotic kidneys presented with a one month history of headache, associated with dizziness and diplopia on horizontal gaze. Examination was significant for profound bilateral 6th nerve palsies. Magnetic resonance imaging showed a hypodense mass that filled the sella and compressed the right cavernous sinus without contacting the optic chiasm. Pituitary function was normal. An endoscopic, transnasal transsphenoidal resection of the lesion was performed; microscopic examination revealed a Rathke’s cleft cyst. Surgical excision resulted in near complete resolution of the bilateral 6th nerve palsy. Rathke’s cleft cysts are an unusual cause of bilateral sixth nerve palsy and represent a potential cause of cranial neuropathy.

Differential diagnosis of ACTH-dependent Cushing’s syndrome often presents major difficulties. Diagnostic troubles are increased by suboptimal specificity of endocrine tests, the rarity of ectopic ACTH secretion and the frequent incidental discovery of pituitary adenomas. A 43-year-old female reported with mild signs and symptoms of hypercortisolism, and initial hormonal tests and results of pituitary imaging (7-mm adenoma) were suggestive for Cushing’s disease. However, inadequate response to corticotrophin-releasing hormone and failure to suppress after 8 mg dexamethasone pointed towards an ectopic source. Total body CT scan visualized only a small, non-specific nodule in the right posterior costophrenic excavation. Inferior petrosal sinus sampling revealed an absent center:periphery ACTH gradient but octreoscan and 18F-FDG-PET-CT failed to detect abnormal tracer accumulation. We weighed results of the laboratory with those of imaging and decided to remove the lung nodule. Pathology identified a typical, ACTH-staining carcinoid and the diagnosis was confirmed by postsurgical hypoadrenalism. In conclusion, imaging may prove unsatisfactory or even misleading for the etiologial diagnosis of ACTH-dependent Cushing’s syndrome and should therefore be interpreted only in context with results of hormonal dynamic testing.

Systemic illnesses are associated with alterations in the hypothalamic–pituitary–peripheral hormone axes, which represent part of the adaptive response to stressful events and may be influenced by type and severity of illness and/or pharmacological therapy. The pituitary gland responds to an acute stressful event with two secretory patterns: adrenocorticotropin (ACTH), prolactin (PRL) and growth hormone (GH) levels increase, while luteinizing hormone (LH), follicle-stimulating hormone (FSH) and thyrotropin (TSH) levels may either decrease or remain unchanged, associated with a decreased activity of their target organ. In protracted critical illness, there is a uniformly reduced pulsatile secretion of ACTH, TSH, LH, PRL and GH, causing a reduction in serum levels of the respective target-hormones. These adaptations are initially protective; however, if inadequate or excessive they may be dangerous and may contribute to the high morbidity and mortality risk of these patients. There is no consensus regarding the type of approach, as well as the criteria to use to define pituitary axis function in critically ill patients. We here provide a critical approach to pituitary axis evaluation during systemic illness.

The activity of the pituitary–adrenal axis can profoundly impact on body composition. This is dramatically seen in Cushing’s syndrome (CS) but changes in body composition are also implicated in depression and alcoholic pseudocushing’s. The pathophysiological mechanisms underlying these changes remain poorly understood. Changes to body composition in CS include increased fat mass, decreased bone mass, thinning of the skin and reduced lean mass. Why these tissues are affected so dramatically is unclear. Additionally, the change in body composition between individuals varies considerably for reasons which are only now becoming evident. This paper reviews the phenotypic changes with altered pituitary–adrenal axis activity and discusses the mechanisms involved. The primary focus is on adipose, bone, muscle and skin since the most dramatic changes are seen in these tissues.