Anterior Pituitary Hormone Deficiencies Research Articles

Clinical experiences and success rates of acromegaly treatment: the single center results of 62 patients.

BackgroundThis study aimed to report the clinical and outcome data from a large cohort of patients diagnosed with acromegaly and treated at our institution over a 20-year period.MethodsSixty-two acromegaly patients (32 women and 30 men) treated and monitored at the endocrinology polyclinic between 1984 and 2013 were enrolled in this retrospective study. Clinical features and patients’ treatment outcomes were evaluated. A level of growth hormone (GH) of <2.5 ng/ml was considered as the criterion for remission, and the normal insulin-like growth factor (IGF) range was based on gender and age.ResultsThe mean age at the time of diagnosis was 38.8 ± 1.4 years, the time to diagnosis was 4.5 ± 0.3 years, and the follow-up duration was 7.3 ± 0.8 years. Among patients’ symptoms, growth in hands and feet and typical facial dysmorphism were the most prominent (92%). The number of patients with diabetes mellitus, hypertension and hyperprolactinemia were 22 (35%), 13 (21%) and 13 (21%), respectively. Microadenomas and macroadenomas were found in eight and 54 patients, respectively. A significant correlation was found between the initial tumor diameters and GH levels (p = 0.002). The mean GH and IGF-1 levels were 39.18 ± 6.1 ng/ml and 993.5 ± 79 ng/ml, respectively. Visual field defect was found in 16 patients (32%). Thirty-one patients were treated by transsphenoidal surgery. Four of these were cured, 10 patients developed postoperative anterior pituitary hormone deficiency, and one patient developed diabetes insipidus. Twenty patients were treated by transcranial surgery, of which two were cured, while 17 patients developed postoperative anterior pituitary hormone deficiency. In total, five of the patients who were not cured after surgery were given conventional radiotherapy, of which two were cured. Four of 15 patients, on whom Gamma Knife radiosurgery was performed, were cured. Biochemical remission was achieved in 32 of 52 patients who received octreotide treatment, and in two of five patients who received lanreotide treatment.ConclusionsThe rate of surgical success in our patients was found to be low. This could be explained by an absence of experienced pituitary surgical centers or surgeons in our region, and the fact that most patients presented late at the macroadenoma stage.

Mutations in NFKB2 and potential genetic heterogeneity in patients with DAVID syndrome, having variable endocrine and immune deficiencies.

BackgroundDAVID syndrome is a rare condition combining anterior pituitary hormone deficiency with common variable immunodeficiency. NFKB2 mutations have recently been identified in patients with ACTH and variable immunodeficiency. A similar mutation was previously found in Nfkb2 in the immunodeficient Lym1 mouse strain, but the effect of the mutation on endocrine function was not evaluated.MethodsWe ascertained six unrelated DAVID syndrome families. We performed whole exome and traditional Sanger sequencing to search for causal genes. Lym1 mice were examined for endocrine developmental anomalies.ResultsMutations in the NFKB2 gene were identified in three of our families through whole exome sequencing, and in a fourth by direct Sanger sequencing. De novo origin of the mutations could be demonstrated in three of the families. All mutations lie near the C-terminus of the protein-coding region, near signals required for processing of NFΚB2 protein by the alternative pathway. Two of the probands had anatomical pituitary anomalies, and one had growth and thyroid hormone as well as ACTH deficiency; these findings have not been previously reported. Two children of one of the probands carried the mutation and have to date exhibited only an immune phenotype. No mutations were found near the C-terminus of NFKB2 in the remaining two probands; whole exome sequencing has been performed for one of these. Lym1 mice, carrying a similar Nfkb2 C-terminal mutation, showed normal pituitary anatomy and expression of proopiomelanocortin (POMC).ConclusionsWe confirm previous findings that mutations near the C-terminus of NFKB2 cause combined endocrine and immunodeficiencies. De novo status of the mutations was confirmed in all cases for which both parents were available. The mutations are consistent with a dominant gain-of-function effect, generating an unprocessed NFKB2 super-repressor protein. We expand the potential phenotype of such NFKB2 mutations to include additional pituitary hormone deficiencies as well as anatomical pituitary anomalies. The lack of an observable endocrine phenotype in Lym1 mice suggests that the endocrine component of DAVID syndrome is either not due to a direct role of NFKB pathways on pituitary development, or else that human and mouse pituitary development differ in its requirements for NFKB pathway function.Electronic supplementary materialThe online version of this article (doi:10.1186/s12881-014-0139-9) contains supplementary material, which is available to authorized users.

PO-0059 Central Diabetes Insipidus In Children: Clinical Profile And Etiologies Monocentric Experience (about 10 Cases)

Introduction Central diabetes insipidus (CDI) or neurohypophyseal diabetes insipidus is a rare disorder in children caused by an inadequate release of the antidiuretic hormone, arginine vasopressin (AVP). CDI is clinically caracterised by polyuria and polydipsia. Methods and materials Clinical, auxological, biological and neuroradiological characteristics of 10 children with central diabetes insipidus (CDI) were retrospectively analysed during a period of 18 years. Results Five girls and five boys with permanent diabetes insipidus were enrolled in the study. The mean age at diagnosis was 6 years five months (range: 4 months -14 years). The major cumulative and often subtle presenting manifestations were: polyuria (n = 10), polydipsia (n = 10), fatigue (n = 2), growth retardation (n = 4), headache (n = 1). All patients had low urine osmolality and elevated plasma osmolality on diagnosis. The aetiology of central DI was organic in 8 patients, craniopharyngioma in 3 patients, Langerhans cell histiocytosis in 2 patients, neurosarcoidosis in one case, Pituitary stalk interruption in one patient and wolfram syndrome in one patient. Three patients had anterior pituitary hormone deficiency and growth hormone deficiency. Polyuria and polydipsia have regressed in all patients put under desmopressin. Patients with craniopharyngioma were operated with a tumour recurrence in one case. Conclusion DIC is a rare disease in Paediatrics. The circumstances of discovery and positive diagnosis are often easy. The underlying aetiology of CDI in children may not initially be obvious. Long-term surveillance is therefore necessary, especially for the early detection of evolving treatable intracranial lesions.

The pituitary gland in patients with Langerhans cell histiocytosis: a clinical and radiological evaluation.

Langerhans cell histiocytosis (LCH) is a rare disease in which the most common endocrine manifestation is diabetes insipidus (DI). Data on anterior pituitary function in patients with LCH are limited. Thus, the present study investigated anterior pituitary function in LCH patients with DI via the evaluation of clinical and radiological findings at disease onset and during follow-up. The present study retrospectively evaluated nine patients with LCH (five males and four females). All diagnoses of LCH were made following histological and/or immunophenotypic analyses of tissue biopsies, bronchoalveolar lavage, or cerebrospinal fluid (CSF). Basal and, if necessary, dynamic pituitary function tests were used to assess anterior pituitary function, and magnetic resonance imaging (MRI) scans were used to image the pituitary. The LCH treatment modality was based on organ involvement. The mean age at onset of DI was 27.6 years (range 15-60 years). One patient (11%) exhibited single organ involvement, while eight patients (89%) displayed multisystem organ involvement. On admittance, one patient had hypogonadotropic hypogonadism, one patient exhibited panhypopituitarism [hypogonadotropic hypogonadism, central hypothyroidism, hypocortisolism, and growth hormone (GH) deficiency], and four patients (44%) displayed hyperprolactinemia. The MRI data revealed infundibular enlargement in seven patients (78%), a thalamic mass in one patient (11%), and the absence of the bright spot in all patients. A single patient (11%) showed a mass in the pons that had a partially empty sella. The patients were treated with radiation therapy (RT), chemotherapy (CT), or a combination of both (RT+CT) and were followed up for a median of 91.8 months (range 2-318 months). Seven patients were assessed during the follow-up period, of whom four patients (57.1%) developed anterior pituitary hormone deficiency, three (43%) were diagnosed with GH deficiency, and one (14%) exhibited gonadotropin deficiency. The gonadotropin deficiency in the patient, which was diagnosed on admittance, was resolved during the follow-up period. DI persisted in all patients, and the conditions of the seven patients who have remained on follow-up are stable. In the present study, patients with LCH exhibited altered function in the anterior pituitary as well as the posterior pituitary, which may be due to the natural course of the disease or the effects of treatment. The present findings indicate that anterior pituitary function should be assessed in LCH patients on admittance and during follow-up, especially in LCH patients with multisystem organ involvement.

Long-Term Outcomes and Complications in Patients With Craniopharyngioma: The British Columbia Cancer Agency Experience

We report long-term outcomes and complications of craniopharyngioma patients referred to our institution. Between 1971 and 2010, 123 consecutive patients received primary treatment for craniopharyngioma in British Columbia and were referred to our institution. The median age was 30 years (range, 2-80 years). Thirty-nine percent of patients were treated primarily with subtotal resection (STR) and radiation therapy (RT), 28% with STR alone, 15% with gross total resection, 11% with cyst drainage (CD) alone, 5% with CD+RT, and 2% with RT alone. Eight percent of patients received intracystic bleomycin (ICB) therapy. Median follow-up was 8.9 years, and study endpoints were reported at 10 years. Ten-year Kaplan-Meier progression-free survival (PFS) was 46%. Patients treated with STR+RT or CD+RT had the highest PFS (82% and 83%, respectively). There were no significant differences between PFS after adjuvant versus salvage RT (84% vs 74%, respectively; P=.6). Disease-specific survival (DSS) was 88%, and overall survival (OS) was 80%. Primary treatment modality did not affect DSS or OS, while older age was a negative prognostic factor for OS but not DSS. Kaplan-Meier rates for visual deterioration, anterior pituitary hormone deficiency, diabetes insipidus, seizure disorder, and cerebrovascular events (CVE) due to treatment, not tumor progression, were 27%, 76%, 45%, 16%, and 11%, respectively. The CVE rate was 29% in patients who received ICB compared to 10% in those who did not (P=.07). We report favorable PFS in patients with craniopharyngioma, especially in those who received RT after surgery. DSS and OS rates were excellent regardless of primary treatment modality. We observed a high incidence of hypopituitarism, visual deterioration, and seizure disorder. Eleven percent of patients experienced CVEs after treatment. There was a suggestion of increased CVE risk in patients treated with ICB.

Surgical biopsies in patients with central diabetes insipidus and thickened pituitary stalks

Thickened pituitary stalks (TPSs) on magnetic resonance imaging (MRI) result from diverse pathologies; therefore, it is essential to make specific diagnoses for clinical decision-making. The diagnoses and indications for surgical biopsies in patients with central diabetes insipidus (CDI) and TPSs are thoroughly discussed in this paper. Thirty-seven patients with CDI and TPSs were retrospectively reviewed. The mean age at the diagnosis of CDI was 29.0 ± 15.9 years (range 8.0-63.3), and the median duration of follow-up was 5.5 ± 2.8 years (range 0.7-13.0). Anterior pituitary hormone deficiencies were documented in 26 (70.3 %) patients. All patients had a TPS on MRI at the diagnosis of CDI, and 21 (56.8 %) patients exhibited radiological changes during the follow-up. Of these 21 patients, 11 exhibited increases in the thickness of the stalk, and two patients exhibited reversals of the TPSs. Involvements of the hypothalamus, pituitary gland, basal ganglia or supersellar, and pineal gland were found in four, three, one, and 1 patient, respectively. Ultimately, clear diagnoses were established in 17 patients who underwent biopsies, nine of whom had germinomas, six of whom had Langerhans cell histiocytosis, one of whom had a granular cell tumor, and one of whom had Erdheim-Chester disease. Patients with CDI and TPSs should submit to periodic clinic follow-ups with serial MRI assessments to establish anterior pituitary deficiencies and to detect radiological progressions that are appropriate for surgical biopsies. Endoscopic-assisted microsurgery via the supraorbital keyhole approach is a good choice for the biopsy of pituitary stalk lesions.

Anterior pituitary hormone deficiency in subjects with total and partial primary empty sella: do all cases need endocrinological evaluation?

To compare anterior pituitary functions between subjects with total and partial primary empty sella (PES) and to assess whether all cases with PES need endocrinological evaluation. Eighty-one subjects with PES (34 total and 47 partial) were included in the study. Basal anterior pituitary and its target hormones were assessed and those with low insulin like growth factor-1 and/or low basal cortisol levels underwent insulin tolerance test (ITT). 67.4% of the subjects with total and 14.9% of those with partial PES had different degrees of hypopituitarism. However, the frequency of hypopituitarism was significantly higher in cases with total PES. The odds ratio (OR) and 95% confidence interval (CI) of secondary hypothyroidism, secondary adrenal, growth hormone and gonadotropin deficiency in subjects with total compared to those with partial PES were as follows: OR = 20.0, 95% CI 4.16 - 95.9, OR = 2.4, 95% CI 1.34 - 5.7, OR = 15.3, 95% CI 4.48 - 52.6 and OR = 10.6, 95% CI 3.37 - 33.5, respectively. A substantial number of subjects with PES, particularly those with total PES, have pituitary hormone deficiency, so regardless of the type of PES, all subjects must be promptly and carefully evaluated for anterior pituitary hormone deficiency.

Chapter 9 - Central regulation of the hypothalamo–pituitary–thyroid (HPT) axis: focus on clinical aspects

The hypothalamus is the most prominent brain region involved in setpoint regulation of the thyroid axis. It generates the diurnal thyroid-stimulating hormone (TSH) rhythm, and it plays a central role in the adaptation of the thyroid axis to environmental factors such as caloric deprivation or infection. Many studies, including studies in human post-mortem tissue samples, have confirmed a key role for the thyrotropin-releasing hormone (TRH) neuron in the hypothalamic paraventricular nucleus (PVN) in thyroid axis regulation. In addition to their negative feedback action on TRH neurons in the hypothalamus, intrahypothalamic thyroid hormones can also modulate metabolism in adipose tissue and the liver via the autonomic nervous system. Congenital or acquired dysfunction of the hypothalamus or pituitary gland may result in central hypothyroidism (CeH). In the Netherlands, the prevalence of permanent congenital CeH as detected by neonatal screening is approximately 1 in 18000. In most neonates congenital CeH is accompanied by additional anterior pituitary hormone deficiencies, and many show clear morphological abnormalities such as a small anterior gland, a thin or absent pituitary stalk, or an ectopic posterior pituitary gland. Recently, a mutation in the immunoglobulin superfamily member 1 (IGSF1) gene was reported as a novel cause of X-linked, apparently isolated CeH occurring in neonates, children and adults. In adults, the most frequent cause of acquired CeH is a pituitary macroadenoma, usually accompanied by other pituitary hormone deficiencies. Central hyperthyroidism is a rare disorder, especially in children. In adults, it is mostly caused by a TSH-secreting pituitary adenoma.

Primary (autoimmune) hypophysitis: a single centre experience

Autoimmune hypophysitis (AH) is a rare autoimmune inflammatory disorder of pituitary gland. To analyse clinical, hormonal, radiological features and management outcomes of AH. Retrospective analysis of patients with primary hypophysitis (where secondary causes of hypophysitis were ruled out) was carried out from 2006 to 2012. AH emerged as the most plausible aetiology and the diagnosis of exclusion. Twenty-four patients with AH (21 females and 3 males) were evaluated. They presented with symptoms of expanding sellar mass (83.3%), symptoms of anterior pituitary hormone deficiencies (58.3%), and diabetes insipidus (16.7%). The anterior pituitary hormonal axes affected were cortisol (75%), thyroid (58.33%) and gonadotropin (50%). All had sellar mass on magnetic resonance imaging, which was symmetrical (91.7%) and homogenously enhancing (91.7%). Stalk thickening, suprasellar extension, loss of posterior pituitary hyperintensity and parasellar T2 dark sign were seen in 87.5, 87.5, 71.5, and 50% respectively. In addition to hormone replacement, five (20.83%) patients underwent trans-sphenoidal surgery, fifteen (62.5%) were watchfully monitored, while four cases (16.67%) received steroid pulse therapy. On follow up imaging, the sellar mass regressed in all, while, stalk thickening was persistent in 13/19 (68.4%) non-operated patients at median follow up of 1 year. Pituitary hormone axis recovery was seen in 10 (41.67%) and was seen in cortisol 10/18 (55.5%) followed by gonadotropin 5/12 (41.67%) axis. Characteristic radiology helps in diagnosis of AH even without tissue diagnosis. Non-operative treatment is the preferred treatment modality. Steroid pulse therapy potentially improves pituitary axis recovery.

Etiology of hypopituitarism in tertiary care institutions in Turkish population: analysis of 773 patients from pituitary study group database

Hypopituitarism in adult life is commonly acquired and the main causes are known as pituitary tumors and/or their treatments. Since there are new insights into the etiology of hypopituitarism and presence of differences in various populations, more studies regarding causes of hypopituitarism are needed to be done in different ethnic groups with sufficient number of patients. Therefore, we performed a multi-center database study in Turkish population investigating the etiology of hypopituitarism in 773 patients in tertiary care institutions. The study was designed and coordinated by the Pituitary Study Group of SEMT (The Society of Endocrinology and Metabolism of Turkey). Nineteen tertiary reference centers (14 university hospitals and 5 training hospitals) from the different regions of Turkey participated in the study. It is a cross-sectional database study, and the data were recorded for 18 months. We mainly classified the causes of hypopituitarism as pituitary tumors (due to direct effects of the pituitary tumors and/or their treatments), extra-pituitary tumors and non-tumoral causes. Mean age of 773 patients (49.8 % male, 50.2 % female) was 43.9 ± 16.1 years (range 16-84 years). The most common etiology of pituitary dysfunction was due to non-tumoral causes (49.2 %) among all patients. However, when we analyze the causes according to gender, the most common etiology in males was pituitary tumors, but the most common etiology in females was non-tumoral causes. According to the subgroup analysis of the causes of hypopituitarism in all patients, the most common four causes of hypopituitarism which have frequencies over 10 % were as follows: non-secretory pituitary adenomas, Sheehan's syndrome, lactotroph adenomas and idiopathic. With regard to the type of hormonal deficiencies; FSH/LH deficiency was the most common hormonal deficit (84.9 % of the patients). In 33.8 % of the patients, 4 anterior pituitary hormone deficiencies (FSH/LH, ACTH, TSH, and GH) were present. Among all patients, the most frequent cause of hypopituitarism was non-secretory pituitary adenomas. However, in female patients, present study clearly demonstrates that Sheehan's syndrome is still one of the most important causes of hypopituitarism in Turkish population. Further, population-based prospective studies need to be done to understand the prevalence and incidence of the causes of hypopituitarism in different countries.

Endocrine dysfunction following traumatic brain injury in acute stage

AimOnly few studies of hormonal dysfunction in acute setting after traumatic brain injury (TBI) are available in literature with variable results. The aim of the present study was to determine the incidence of anterior pituitary hormone deficiencies, and correlate with in hospital mortality. MethodsThis study was carried out on 30 patients with moderate to severe TBI presenting within 24 h of injury. Chemiluminiscence immunoassay using an automated chemiluminiscence analyser was used to determine the basal hormone levels. Thyroid stimulating hormone (TSH), prolactin (PRL), cortisol, growth hormone (GH), and testosterone in males or luteinizing hormone (LH) and follicle stimulating hormone (FSH) in females were measured. ResultsOut of the 30 cases, 12 cases underwent surgery for various reasons. Six patients expired, and all of them had a poor GCS at presentation (mean 4.8 ± 0.9). In the acute setting high cortisol level showed a trend towards significance (p = 0.097) in terms of mortality. Other hormonal levels were also found to be abnormal, but no conclusion could be drawn due to small number. ConclusionAnterior pituitary hormone imbalance is common after TBI in acute setting. Elevated cortisol is associated with increased mortality.

The causes of hypopituitarism in the absence of abnormal pituitary imaging

Hypopituitarism in the absence of a history of pituitary pathology or abnormal pituitary imaging is rare. To identify the cause of hypopituitarism in individuals in whom pituitary imaging was normal. Retrospective analysis of electronic patient record. A review of the pituitary function in the 506 patients on the Morriston Hospital pituitary database revealed 230 had some degree of hypopituitarism and of these, 21 (9%) had normal pituitary imaging. Of this group, six patients had a past medical history of subarachnoid haemorrhage, head injury or meningitis, and mainly suffered from a deficiency of antidiuretic hormone. One patient had a stroke resulting in multiple anterior hormone deficiencies and six individuals had idiopathic cranial diabetes insipidus (DI). Subsequent investigations of the remaining eight patients with normal pituitary imaging revealed that two had neurosarcoidosis both of whom had panhypopituitarism. Four patients had haemochromatosis which resulted in gonadotropin deficiency in two, DI in one and panhypopituitarism in the other. There were two individuals with confirmed hypopituitarism and multiple hormone deficiencies in which no cause could be identified. These results show that hypopituitarism in the absence of pituitary pathology or an identifiable cause is rare. In patients with multiple anterior pituitary hormone deficiencies haemochromatosis and sarcoidosis should be considered.

Index of Suspicion in the Nursery

A term male infant is transferred to the NICU for persistent hypoglycemia at age 3.5 hours. The infant had a blood sugar level of 21 mg/dL at age 3 hours and despite refeeding 20 mL of 20 calories per ounce of formula, his blood glucose level remained at 20 mg/dL at 3.5 hours. The infant was born via cesarean delivery for a nonreassuring heart rate tracing to a 19-year-old G1P 0 African-American mother. All prenatal laboratory results were negative, including an oral glucose tolerance test. Prenatal ultrasonography was performed during the second trimester and showed no gross fetal anomalies other than the presence of a two-vessel cord. The infant cried spontaneously at birth and had some transient respiratory distress. The infant weighs 2,960 g (50th percentile) with a length of 48 cm (50th percentile) and a head circumference of 32.5 cm (25th–50th percentile). Results of the physical examination are normal except for a small penis (stretched penile length of 1.5 cm, width of 0.6 cm) and an undescended left testicle. Blood glucose levels below 40 mg/dL persist despite two boluses of 10% dextrose and administration of continuous dextrose infusion with a glucose infusion rate of ∼5 mg/kg per minute. Glucose levels above 40 mg/dL are eventually achieved with a glucose infusion rate of 8 mg/kg per minute. The pediatric endocrinology service was consulted on the second day for persistent hypoglycemia. A 3,490-g term male infant is born to a 20-year-old primigravida mother. She received good prenatal care, and her pregnancy was uncomplicated. Antenatal screening for human immunodeficiency virus, hepatitis B, and syphilis were negative, and she had immunity against rubella. Results of the patient’s cervical culture were positive for group B streptococcus, but she received adequate intrapartum penicillin prophylaxis before delivery. There was no abnormality noted on the fetal cardiotocography. …

Baseline characteristics and effects of ten years of growth hormone (GH) replacement therapy in adults previously treated with pituitary irradiation

ContextLittle is known of the importance of previous irradiation therapy for baseline characteristics and responsiveness to GH replacement in GH deficient (GHD) adults. Objective/design/patientsIn this prospective, single-centre, open-label study, the effects of 10-year GH replacement were determined in 18 GHD adults that had previously received conventional external fractionated pituitary irradiation therapy (IRR group) and 18 non-irradiated GHD patients (non-IRR group). All patients had adult onset disease and complete deficiency of anterior pituitary hormones and both groups were comparable in terms of age, gender, body mass index (BMI), and waist:hip ratio. ResultsAt baseline, IRR patients had higher serum triglyceride (TG) and insulin levels and lower high density lipoprotein (HDL)-cholesterol (HDL-C) level than non-IRR patients (all p<0.05). The 10-year GH replacement improved body composition, bone mass and serum lipid profile without any between-group differences, except for a marginally more beneficial response in serum TG level in the IRR patients. After 10years, there was no between-group difference in any variable after correction for a higher replacement dose of glucocorticoids in the IRR patients at study end using an analysis of covariance. During the 10-year GH replacement, 5 IRR patients suffered from vascular events (2 fatal) whereas only one non-fatal vascular event occurred in the non-IRR patients. ConclusionsIRR patients with GHD display a more severely impaired cardiovascular risk profile at baseline, which was reversed by the 10-year GH replacement after correction for the higher glucocorticoid dose at study end. However, vascular events occurred more frequently in the IRR patients.

Clinical characteristics of central diabetes insipidus in Taiwanese children

Data on the clinical features of children with central diabetes insipidus (CDI) are lacking in Taiwan. This study investigated the clinical manifestations and etiology of CDI in Taiwanese children. From 1983 to 2012, 62 children with permanent diabetes insipidus were enrolled in the study. They were diagnosed at the Department of Pediatrics of National Taiwan University Hospital. Their medical records were thoroughly reviewed and their clinical symptoms and signs, laboratory data, and etiologies were analyzed. The patients' median age at diagnosis was 10 years and the median interval between initial manifestations and diagnosis was 0.5 years. The most common symptoms and signs were polyuria, polydipsia, nocturia, and growth retardation. Most patients had low urine osmolality and elevated plasma osmolality on diagnosis. Absence of a posterior pituitary hyperintense signal and thickening of the pituitary stalk were common findings on magnetic resonance imaging. Approximately 80% of the patients had anterior pituitary hormone deficiency and all patients had growth hormone deficiency. Approximately 60% of patients had intracranial lesions, the most common causes of which were germ cell tumor and Langerhans cell histiocytosis. Two patients were initially believed to have idiopathic CDI but intracranial lesions were detected during the follow-up period. Because a delayed diagnosis of CDI is common in Taiwanese children, a high index of suspicion is important. The underlying etiology of CDI in children may not initially be obvious. Long-term surveillance is therefore necessary, especially for the early detection of evolving treatable intracranial lesions.

Pituitary stalk interruption syndrome in 58 Chinese patients: clinical features and genetic analysis

Pituitary stalk interruption syndrome (PSIS) is rare and its clinical features and pathogenesis are poorly understood. This study characterized the clinical and genetic features of PSIS in Chinese patients. Clinical data of 58 patients with PSIS and 46 patients with GH deficiency but a normal pituitary stalk (NPS) were retrospectively analysed. HESX1, LHX4, OTX2 and SOX3 polymorphisms were screened in 33 PSIS patients, and GH1 and GHRHR in 4 NPS patients. Deficiency of GH was 100% in both PSIS and NPS groups. Other deficiency rates for PSIS and NPS groups were as follows: ACTH, 77·6% and 23·9%; TSH, 43·1% and 10·9%; LH/FSH, 94·2% and 47·4%; and combined pituitary hormone, 93·1% and 41·3% respectively. In PSIS and NPS patients, the percentages of anterior pituitary hypoplasia were 98·3% and 54·3%, pituitary stalk abnormality were 100% and 0%, and ectopic neurohypophysis were 91·4% and 0%. A novel heterozygous sequence variant (c.142A>T, p.T48S) was found in HESX1 in one PSIS patient, 3 polymorphisms (c.63T>C, p.G21G; c.450C>T, p.N150N; and c.983A>G, p.N328S) in LHX4 in 7, 1 and 31 PSIS patients, respectively, and a hemizygous polymorphism (c.157G>C, p.V53L) in SOX3 in one PSIS patient. No OTX2 abnormality was detected in PSIS patients, and no GH1 or GHRHR polymorphisms in NPS patients. Compared with NPS, PSIS patients had more severe anterior pituitary hormone deficiency, lower anterior pituitary hormone secretion and higher probability of abnormal pituitary morphology. HESX1, LHX4 and SOX3 polymorphisms may be associated with PSIS.

Acute Diabetes Insipidus Mediated by Vasopressinase After Placental Abruption

Postpartum, diabetes insipidus (DI) can be part of Sheehan's syndrome or lymphocytic hypophysitis in combination with anterior pituitary hormone deficiencies. In contrast, acute onset of isolated DI in the postpartum period is unusual. This patient presented at 33 weeks gestation with placental abruption, prompting a cesarean delivery of twins. Immediately after delivery, she developed severe DI. The DI could be controlled with the vasopressinase-resistant 1-deamino-8-D-arginine vasopressin (DDAVP), but not with arginine vasopressin (AVP), and it resolved within a few weeks. The aim of this study was to demonstrate that the postpartum DI in this patient was caused by the release of placental vasopressinase into the maternal bloodstream. Cells were transiently transfected with the AVP receptor 2 (AVPR2) and treated with either AVP or DDAVP in the presence of the patient's serum collected postpartum or 10 weeks after delivery. The response to the different treatments was evaluated by measuring the activity of a cAMP-responsive firefly luciferase reporter construct. The in vitro studies demonstrate that the patient's postpartum serum disrupts activation of the AVPR2 by AVP, but not by the vasopressinase-resistant DDAVP. Placental abruption can rarely be associated with acute postpartum DI caused by release of placental vasopressinase into the bloodstream. This clinical entity must be considered in patients with placental abruption and when evaluating patients presenting with DI after delivery.

Epidemiology and aetiologies of hypopituitarism

Anterior Pituitary Hormone Deficiencies may be due to any lesion in this anatomical region, most commonly benign tumors like pituitary adenomas or craniopharyngiomas, and to surgical or radiation-based treatments of these tumors. Less frequently, cranial traumas, inflammatory or autoimmune processes like lymphocytic hypophysitis or genetic defects may cause pituitary deficits. The resulting pituitary hormone deficiencies may lead to severe clinical consequences with significant morbidity and often increased mortality despite recent therapeutic improvements. The large observational studies launched for the follow-up of patients treated by growth hormone have provided valuable epidemiological data. In recent years, new aetiologies of acquired hypopituitarism have been reported such as hypophysitis following targeted anticancer immune therapies. Hypopituitarism however remains predominantly a consequence of benign pituitary tumors and of their treatments.

Solitary median maxillary central incisor, a clinical predictor of hypoplastic anterior pituitary, ectopic neurohypophysis and growth hormone deficiency

Solitary median maxillary central incisor, a clinical predictor of hypoplastic anterior pituitary, ectopic neurohypophysis and growth hormone deficiency

Low and Normal IGF-1 Levels in Patients with Chronic Medical Disorders(CMD) is Independent of Anterior Pituitary Hormone Deficiencies: Implications for Treating IGF-1 Abnormal Deficiencies with CMD

Over time, based on evidence-based medicine, a number of hormonal test levels including IGF-1 had been raised or lowered to meet new criteria standards. In particular, IGF-1 plasma levels have been shown in several studies to be an independent diagnostic tool in Adult Growth Hormone Deficiency (AGHD). Many endocrinology studies link low IGF-1 plasma levels with low levels of other anterior pituitary hormones (i.e., LH, FSH, and TSH). Low IGF-1 is considered by most to be between 84-100 µ/l and numerous studies recommend that raising IGF-1 to high normal range reverses Chronic Medical Diseases (CMD), improves bone mineral density (BMD), and fibromyalgia. Moreover, some studies suggest that low levels of IGF-1 by itself independent of anterior pituitary deficiencies is sufficient to determine AGHD in humans. In order to determine the relationship of low IGF-1 with that of LH, FSH, and TSH levels in subjects with CMD, we evaluated these levels (± SD) in 944 patients. Patients with IGF-1 below 84 µ/l, 100 µ/l, and 150 µ/l were accessed. 9.22% had less than 84 µ/l (SD ± 12.52); 19.9% had less than 100 µ/l (SD ± 9.54); and 51.6 had less than 150 µ/l (SD ± 26.0). Specifically, the percentages found for low LH, FSH, and TSH were only 4.2%, 4.8%, and 6.5%. We conclude that IGF-1 deficiencies occur independent of comorbid deficiencies of LH, FSH, and TSH. Finally, we propose that based on the present investigation, IGF-1 low levels between the range of 84-100 µ/l may be too low to be considered as an independent diagnostic marker to treat AGHD with CMD.