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Context Nationwide data on children diagnosed with craniopharyngioma (CP) are not available in Italy. Objective This work aimed to identify patients’ characteristics, type of surgical approach, complications and recurrences, number of pituitary deficits, and number of patients starting growth hormone (GH) treatment. Methods A retrospective multicenter collection took place of 145 patients aged 0 to 18 years who underwent surgery for CP between 2000 and 2018, and followed up in 17 Italian centers of pediatric endocrinology. Results Age at diagnosis was 8.4 ± 4.1 years. Duration of symptoms was 10.8 ± 12.5 months and headache was most frequent (54%), followed by impaired growth (48%) and visual disturbances (44%). Most lesions were suprasellar (85%), and histology was adamantinomatous in all cases but two. Surgical approach was transcranial (TC) in 67.5% of cases and transsphenoidal (TS) in 31.%. The TC approach was prevalent in all age groups. Postsurgery complications occurred in 53% of cases, with water-electrolyte disturbances most frequent. Radiotherapy was used in 39% of cases. All patients but one presented with at least one hormone pituitary deficiency, with thyrotropin deficiency most frequent (98.3%), followed by adrenocorticotropin (96.8%), arginine vasopressin (91.1%), and GH (77.4%). Body mass index (BMI) significantly increased over time. A hypothalamic disturbance was present in 55% of cases. GH therapy was started during follow-up in 112 patients at a mean age of 10.6 years, and 54 developed a recurrence or regrowth of the residual lesion. Conclusion CP is often diagnosed late in Italy, with TC more frequent than the TS surgical approach. Postsurgery complications were not rare, and hypopituitarism developed almost in all cases. BMI shows a tendency to increase overtime.

In some cases, Empty sella syndrome (ESS) is associated with pituitary deficiency. Although it is well known that pituitary hormones have effects on in many organs and systems, few studies have addressed the relationship between hypopituitarism and heart/arrhythmia. This unusual situation leads to discussion of the possible causes and management. We present a case of a 19-year-old male with an onset of cardiac arrhythmia was finally diagnosed as hypopituitarism. The patient recovered quickly by the means of hydrocortisone therapy. Most of pituitary hormones returned to normal, as well as no ventricular arrhythmia occurred any more. Good outcomes were observed that suggesting pituitary hormones may have effects on cardiac conduction system. However, the exact mechanisms need to be further studied.

Clinicians face many challenges regarding conception and pregnancy management for women with panhypopituitarism. Fertility in women with panhypopituitarism is often reduced, and they are at risk of obstetric complications. The authors describe the case of a woman with congenital panhypopituitarism who had a successful pregnancy after ovulation induction and optimization of hormonal replacement therapy. This case report emphasizes the importance of careful adjustment of hormonal replacement therapy in managing pregnant women with panhypopituitarism., Highlights • Successful pregnancy is possible in women with panhypopituitarism. • Women with panhypopituitarism are at risk of obstetric complications. • Management of panhypopituitarism during pregnancy requires a multidisciplinary approach.

Pituitary stalk interruption syndrome is a rare disease characterized by a deficiency of adenohypophyseal hormones. Clinical presentation usually occurs in childhood or in the second decade of life. The severity of hormonal deficiency is variable. It may be isolated or be accompanied by extra–pituitary anomalies. Magnetic resonance imaging findings are considered as an absent pituitary stalk, absent or smaller adenohypophysis, absent or ectopic neurohypophysis. Contrast-enhanced imaging is essential in evaluating the presence and morphology of the pituitary stalk. In the presence of clinical findings, evaluation of the hypothalamic–pituitary region using magnetic resonance imaging is necessary for diagnosis. Early diagnosed cases can maintain their normal lives with hormone replacement. In this article, we aimed to present pituitary stalk interruption syndrome and its magnetic resonance imaging findings with a case presentation

Objective: Sheehan’s syndrome is pituitary deficiency induced by intrapartum and postpartum hemorrhage and hypovolemia. It is still frequent in underdeveloped and developing countries. Sheehan’s syndrome is one of the reason of empty sella. The symptoms of the syndrome can be seen months to years later depend on the degree of pituitary damage. History of postpartum hemorrhage, failure to lactate and cessation of menses are important clues to the diagnosis. Early diagnosis and appropriate treatment are very important to reduce morbidity and mortality of the patients. Case: In this study sheehan’s syndrome which led to auto pan-hypopituitarism and developed gradually in a patient with sheehan‘s syndrome which in this case, delivered a baby at home 27 years ago and had severe postpartum hemorrhage will be presented. And this 63-year-old female patient was diagnosed as Sjogren’s syndrome and sheehan syndrome by clinical and laboratory findings for the purpose of further investigation and treatment because of symptoms of fever and anemia

Nuclear factor kappa-B subunit 2 (NF-κB2/p100/p52), encoded by NFKB2 (MIM: 164012) belongs to the NF-κB family of transcription factors that play a critical role in inflammation, immunity, cell proliferation, differentiation and survival. Heterozygous C-terminal mutations in NFKB2 have been associated with early-onset common variable immunodeficiency (CVID), central adrenal insufficiency and ectodermal dysplasia. Only two previously reported cases have documented decreased natural killer (NK) cell cytotoxicity, and little is known about the role of NF-κB2 in NK cell maturation and function. Here we report a 13-year-old female that presented at 6 years of age with a history of early onset recurrent sinopulmonary infections, progressive hair loss, and hypogamaglobulinemia consistent with a clinical diagnosis of CVID. At 9 years of age she had cytomegalovirus (CMV) pneumonia that responded to ganciclovir treatment. Functional NK cell testing demonstrated decreased NK cell cytotoxicity despite normal NK cell numbers, consistent with a greater susceptibility to systemic CMV infection. Research exome sequencing (ES) was performed and revealed a novel de novo heterozygous nonsense mutation in NFKB2 (c.2611C>T, p.Gln871*) that was not carried by either of her parents. The variant was Sanger sequenced and confirmed to be de novo in the patient. At age 12, she presented with a reactivation of the systemic CMV infection that was associated with severe and progressive nephrotic syndrome with histologic evidence of pedicellar effacement and negative immunofluorescence. To our knowledge, this is the third NF-κB2 deficient patient in which an abnormal NK cell function has been observed, suggesting a role for non-canonical NF-κB2 signaling in NK cell cytotoxicity. NK cell function should be assessed in patients with mutations in the non-canonical NF-κB pathway to explore the risk for systemic viral infections that may lead to severe complications and impact patient survival. Similarly NF-κB2 should be considered in patients with combined immunodeficiency who have aberrant NK cell function. Further studies are needed to characterize the role of NF-κB2 in NK cell cytotoxic function.

Pituitary dysfunction following traumatic brain injury (TBI) is significant and rarely considered by clinicians. This topic has received much more attention in the last decade. The incidence of post TBI anterior pituitary dysfunction is around 30% acutely, and declines to around 20% by one year. Growth hormone and gonadotrophic hormones are the most common deficiencies seen after traumatic brain injury, but also the most likely to spontaneously recover. The majority of deficiencies present within the first year, but extreme delayed presentation has been reported. Information on posterior pituitary dysfunction is less reliable ranging from 3%-40% incidence but prospective data suggests a rate around 5%. The mechanism, risk factors, natural history, and long-term effect of treatment are poorly defined in the literature and limited by a lack of standardization. Post TBI pituitary dysfunction is an entity to recognize with significant clinical relevance. Secondary hypoadrenalism, hypothyroidism and central diabetes insipidus should be treated acutely while deficiencies in growth and gonadotrophic hormones should be initially observed.

WOS: 000316925400004, PubMed ID: 23245206, Sheehan's syndrome (SS) is characterized by various degrees of hypopituitarism, and develops as a result of ischemic pituitary necrosis due to severe postpartum hemorrhage. Increased pituitary volume, small sella size, disseminated intravascular coagulation and autoimmunity are the proposed factors in the pathogenesis of SS. Hormonal insufficiencies, ranging from single pituitary hormone insufficiency to total hypopituitarism, are observed in patients. The first most important issue in the diagnosis is being aware of the syndrome. Lack of lactation and failure of menstrual resumption after delivery that complicated with severe hemorrhage are the most important clues in diagnosing SS. The most frequent endocrine disorders are the deficiencies of growth hormone and prolactin. In patients with typical obstetric history, prolactin response to TRH seems to be the most sensitive screening test in diagnosing SS. Other than typical pituitary deficiency, symptoms such as anemia, pancytopenia, osteoporosis, impairment in cognitive functions and impairment in the quality of life are also present in these patients. Treatment of SS is based on the appropriate replacement of deficient hormones. Growth hormone replacement has been found to have positive effects; however, risk to benefit ratio, side effects and cost of the treatment should be taken into account.

International audience; Gamma Knife radiosurgery (GK) is an effective treatment for hypothalamic hamar-toma. No precise data are available on the risk of endocrine side effects of this treatment. In this study, 34 patients with hypothalamic hamartoma (HH) were followed prospectively at the Department of Endocrinology, La Timone Hospital, Marseille, France, for a mean follow-up of >2 years (mean AE standard deviation [SD] 3.6 AE 2 years). Initial pre-and post-GK radiosurgery evaluations were performed, including weight, body mass index (BMI), and a complete endocrinological workup. At diagnosis, eight patients presented with central precocious puberty at a mean age of 5.4 AE 2.4 years. At the time of GK (mean age 18.2 AE 11.1 years), two patients previously treated with surgery presented with luteinizing hormone/follicle-stimulating hormone (LH/FSH) deficiency. After GK, only one patient presented with a new thy-rotropin-stimulating hormone (TSH) deficiency, 2 years after the procedure. The other pituitary axes remained normal in all but two patients (who had LH/FSH deficiency prior to GK). There was no significant difference between pre-and post-GK mean BMI (26.9 vs. 25.1 kg/m 2 , p = 0.59). To conclude, in this group of 34 patients, GK did not induce major endocrinologic side effects reported with all the other surgical techniques in the literature. It is, thus, a safe and effective procedure in the treatment of hypothalamic hamartoma.

Background and purpose Aneurysmal subarachnoid hemorrhage (SAH) survivors often complain of fatigue, which is disabling. Fatigue is also a common symptom of pituitary dysfunction (PD), in particular in patients with growth hormone deficiency (GHD). A possible association between fatigue after SAH and long-term pituitary deficiency in SAH survivors has not yet been established. Methods A single center observational study was conducted amongst 84 aneurysmal SAH survivors to study the relationship between PD and fatigue over time after SAH, using mixed model analysis. Fatigue was measured with the Fatigue Severity Scale and its relationships with other clinical variables were studied. Results Three-quarters of respondents (76%) have pathological fatigue directly after SAH and almost two-thirds (60%) of patients still have pathological levels of fatigue after 14 months. The severity of SAH measured with a World Federation of Neurosurgical Societies (WFNS) score higher than 1 (P = 0.008) was associated with long-term fatigue. There is no statistically significant effect of PD (P = 0.8) or GHD (P = 0.23) on fatigue in SAH survivors over time. Conclusions Fatigue is a common symptom amongst SAH survivors. WFNS is a usable clinical determinant of fatigue in SAH survivors. Neither PD nor GHD has a significant effect on long-term fatigue after SAH.

Adrenal and pituitary deficiency can present catastrophically with shock and cardiopulmonary arrest or gradually with lethargy and failure to thrive. Lifesaving treatment is safe and simple, and timely recognition of the disorder minimizes the likelihood of death or permanent brain injury from hypoglycemia and hypothyroidism. This article reviews the major causes and clinical presentations of adrenal and pituitary deficiency states in the newborn period as well as evaluation of pituitary and adrenal function and the principles of endocrine replacement therapy.

Objective: To study pregnancies in a large group of patients with growth hormone deficiency and hypopituitarism; and to investigate potential factors determining pregnancy outcomes and pregnancy complications. Design: We analyzed pregnancies reported in KIMS, the Pfizer International Metabolic Database, of adult patients with growth hormone deficiency treated with growth hormone. Setting: Outpatient clinics. Patient(s): A total of 201 pregnancies were reported: 173 in female patients and 28 in partners of male patients. Intervention(s): Growth hormone replacement therapy (GHRT) was prescribed according to the local clinical practice. Main Outcome Measure(s): Pregnancy outcomes (live births, gestational week at delivery, and birth weight), pregnancy complications, and their relationship to use of GHRT during pregnancy were analyzed with regression models. Result(s): Two-thirds of women underwent fertility treatment to achieve pregnancy. Growth hormone replacement therapy was stopped before pregnancy in 7.5% of the female patients, as soon as pregnancy was confirmed in 40.1%, and at the end of the second trimester in 24.7% of the patients, whereas 27.6% continued GHRT throughout pregnancy. Birth of a healthy child was reported in 79% of the female pregnancies, nonelective abortions occurred mainly in the first trimester, and one fetal malformation (cystic hygroma) was diagnosed in the second trimester. Pregnancy outcomes and pregnancy complications were not related to GHRT treatment patterns, method of conception, or number of additional pituitary deficiencies. Conclusion(s): These data on pregnancy outcomes in a large group of women with hypopituitarism revealed no relationship between GHRT regimens and pregnancy outcomes. (C) 2015 by American Society for Reproductive Medicine.

The classical method of skeletal age assessment is based on the recognition of changes in the radiographic appearance of the maturity indicators in hand-wrist radiographs by comparison with a reference atlas. The purpose of this study was the evaluation of the possibility to assess bone age using a less invasive method such as dual-energy X-ray absorptiometry (DXA). Bone ages of 50 children free of any chronic diseases (5-18 years old) and ten with multihormonal pituitary deficiency (MPD) (8-20 years old) were assessed using an Expert-XL densitometer. Hand scans and classical hand-wrist radiographs were evaluated by two independent observers for bone age by visual comparison with reference standards of skeletal development published in the atlas. The precision errors of duplicate bone age ratings were low both for radiographs (1%) and DXA hand scans (0.9%). A high degree of agreement between bone age ratings done by two observers was assessed by intraclass correlation coefficients. The same bone age based on radiographs and DXA hand scans was assessed in 44 of 60 cases (73.3%); in 16 cases the differences between bone age were no higher than 0.5 year. No significant difference between mean bone age based on radiographs and DXA hand scans was observed ( P0.05). Moreover, there was a very strong correlation between bone age results ( r=0.998; r(2)=0.996; P0.0001), indicating agreement of bone age assessments based on DXA and radiographic images. Remarkable differences (up to 3 years) between bone age and chronological age were observed in healthy subjects, probably reflecting the effect of the secular trend towards earlier maturation or alterations in pubertal development. The study indicates that evaluation of skeletal maturity using DXA images is less invasive (up to 8 micro Sv) than radiography, giving results comparable to the classical method.

A distinct form of Moebius sequence is associated with hypogonadotrophic hypogonadism. There have been five such cases to date. We now add a further case with detailed neurologic, endocrine, and autopsy findings and offer a hypothesis drawing parallels with the already established basis of hypogonadotrophic hypogonadism in the X-linked form of Kallman syndrome.

Clinical presentation of pituitary adenomas is influenced by age of patients and stage of the tumour at diagnosis. In this study we intended to analyse the features of pituitary adenomas in old patients. Subjects and Methods: It is a retro- and prospective study concerning 37 patients aged 60 years and over harbouring a pituitary adenoma. Patients with giant and/or invasive tumours which means tumours ≥ 40 mm or tumours invading the cavernous sinuses (G1) were compared to patients with tumours < 40 mm without cavernous sinuses involvement (G2). Results: 38% (N=14) of the tumours were giants and/or invasive, the adenoma size was 40.53 ± 11.38 mm in G1 (with involvement of cavernous sinuses in 16%) and 22.7 ± 7.96 mm in G2, patients of G1 were older than those of G2: 70.71 ± 6.70 years vs 66.17 ± 5.41 years. Neuro-ophthalmological manifestations were appealing in 78% in G1 and 61% in G2; the tumour was incidentally discovered in 21% in G2 and 7% in G1. No secreting adenomas were the more prevalent in the two groups (64% in G1 and 61% in G2); GH secreting adenomas were recorded only in G2. Pituitary deficiency wasn’t different between the two groups (61% in G1 vs 60% in G2). Severe visual loss was more prevalent in G1 than G2: 71% vs. 33%. Conclusion: Pituitary adenomas in the elderly are often large and invasive, predominantly no secreting and frequently diagnosed late at an advanced stage of visual loss and pituitary deficiency.

Objective Poor outcome and neuropsychological sequelae after aneurysmal subarachnoid hemorrhage (SAH) is a persistent problem. Pituitary dysfunction has been proposed as a contributing factor. Clinical studies have given variable and conflicting results on its importance and incidence after SAH. The aim of this study was to prospectively examine SAH patients with assessment of endocrine function in the acute stage and at early follow-up and to compare clinical SAH features to endocrine abnormalities indicating pituitary dysfunction. Methods Endocrine function was assessed by basal hormonal concentrations at 5 to 10 days and 3 to 6 months after SAH. Growth hormone deficiency also was evaluated by the growth hormone releasing hormone–arginine stimulation test at follow-up. Clinical outcome was assessed and scored according to the Glasgow Outcome Scale. Results Fifty-one SAH patients were included and assessed in the acute stage after the bleed. Six were lost to follow-up. The overall prevalence of pituitary dysfunction was 37% and 27% in the acute stage and at follow-up, respectively. Patients with evidence of pituitary dysfunction had significantly worse outcome according to Glasgow Outcome Scale at both occasions. The ruptured aneurysm was more commonly located in the circle of Willis among patients with pituitary dysfunction in the acute stage. Conclusions The present results support earlier findings that hormonal abnormalities are not infrequent after SAH. Furthermore, our data suggest that pituitary dysfunction is associated with worse clinical outcome and is more common among patients with bleeding sites close to the hypothalamus.

It is now widely accepted that brain injuries are often the cause of acquired hypopituitarism in adulthood. The information about the pituitary function in brain-injured children and adolescence is however scanty. An international workshop entitled “Traumatic brain injury and hypopituitarism” was held on 9–10 April 2006 in Granada, Spain, in order to explore the relatively unknown but potentially important field of investigation, diagnosis and treatment of pituitary deficiency in children and adolescents following traumatic brain injury (TBI). The following conclusions were reached: 1) a prospective pediatric and adolescent study of pituitary function was indicated; 2) close collaboration among neurosurgeons, neurologists, rehabilitation specialists and pediatric endocrinologists, with support from adult endocrinologists, is essential to achieve a coordinated approach to the care of children after TBI; 3) a model of interaction, similar to that now existing with oncologists, needs to be established; 4) a “pediatric TBI late-effects” service should be created, preferably led by endocrinologists, so that knowledge of growth and puberty can be included, in order to optimize identification, investigation and treatment of this important group of patients.

The effects of growth hormone (GH) treatment on 24-h energy expenditure (EE) were studied in a open trial over a period of 4 weeks. Five subjects, four men and one woman, with a history of complete GH deficiency were included. All the subjects were examined on 2 consecutive days on baseline and, thereafter, at six occasions during a period of 1 month (days 1, 2, 5, 8, 15, and 30). The dose of GH was 0.25 U/kg·week, administered sc once a day in the evening. EE was determined in a chamber for indirect calorimetry. Body composition was determined with dual-energy x-ray absorptiometry and computed tomography using a four-scan technique. Blood samples were examined using well-established RIAs. During the first 2 weeks, 24-h EE increased by 6 ± 3% (range 1–8%) from 40.9 ± 4.8 to 42.9 ± 4.8 kcal/24 h·kg (P < 0.05), sleeping metabolic rate by 14 ± 3% (range 10–18%) from 28.4 ± 1.9 to 32.9 ± 2.2 kcal/24h·kg (P < 0.001), and basal metabolic rate by 11 ± 7% (range 0–18%) from 29.6 ± 2.4 to 33.3 ± 2.6 kcal/24h·kg (P < 0.05). No change was found in daytime EE. The increase in EE covaried with changes in insulin-like growth factor 1, the free T3/free T4 ratio, insulin-like growth factor-binding protein-3, and the aminoterminal procollagen III peptide but not with changes in body composition. It is suggested that the stimulating effect of GH on EE occurs gradually during a 2-week period and is only detectable during night and morning hours, when significant levels of GH occur.

Background Over the last few years, awareness and detection rates of hypopituitarism following traumatic brain injury (TBI) and subarachnoid hemorrhage (SAH) has steadily increased. Moreover, recent studies have found that a clinically relevant number of patients develop pituitary insufficiency after intracranial operations and radiation treatment for non-pituitary tumors. But, in a substantial portion of more than 40%, the hypopituitarism already exists before surgery. We sought to determine the frequency, pattern, and severity of endocrine disturbances using basal and advanced dynamic pituitary testing following non-pituitary intracranial procedures. Methods 51 patients (29 women, 22 men) with a mean age of 55 years (range of 20 to 75 years) underwent prospective evaluation of basal parameters and pituitary function testing (combined growth hormone releasing hormone (GHRH)/arginine test, insulin tolerance test (ITT), low dose adrenocorticotropic hormone (ACTH) test), performed 5 to 168 months (median 47.2 months) after intracranial operation (4 patients had additional radiation and 2 patients received additional radiation combined with chemotherapy). Results We discovered an overall rate of hypopituitarism with distinct magnitude in 64.7% (solitary in 45.1%, multiple in 19.6%, complete in 0%). Adrenocorticotropic hormone insufficiency was found in 51.0% (partial in 41.2%, complete in 9.8%) and growth hormone deficiency (GHD) occurred in 31.4% (partial in 25.5%, severe in 5.9%). Thyrotropic hormone deficiency was not identified. The frequency of hypogonadism was 9.1% in men. Pituitary deficits were associated with operations both in close proximity to the sella turcica and more distant regions (p = 0.91). Age (p = 0.76) and gender (p = 0.24) did not significantly differ across patients with versus those without hormonal deficiencies. Groups did not significantly differ across pathology and operation type (p = 0.07). Conclusion Hypopituitarism occurs more frequently than expected in patients who have undergone neurosurgical intracranial procedures for conditions other then pituitary tumors or may already exists in a neurosurgical population before surgery. Pituitary function testing and adequate substitution may be warranted for neurosurgical patients with intracranial pathologies at least if unexplained symptoms like fatigue, weakness, altered mental activity, and decreased exercise tolerance are present.

Abnormalities of the hypothalamo-hypophyseal axis are frequently associated with pituitary deficiency. We describe a previously unknown morphological presentation of the ectopic posterior neurohypophyseal “bright spot.”

We highlight the diagnostic consideration of lymphocytic adenohypophysitis (LAH) in the postpartum patient with unexplained partial pituitary insufficiency. Further, we emphasize that in patients with a normal magnetic resonance imaging scan, the measurement of antipituitary antibodies (APA) may provide an alternative means of confirming the diagnosis. Finally, although assays of APA are nonstandardized, intensive study and development of a reliable APA assay could promote our understanding of the autoimmune process, eventually facilitating the diagnosis of LAH and eliminating the need for biopsy.

A 14.8-year-old girl was treated with bromocriptine for a prolactin-secreting adenoma. She suddenly developed headaches, vomiting, fever and meningeal syndrome. This was associated with corticotropin, thyrotropin and gonadotropin deficiencies. Magnetic resonance imaging showed peripheral enhancement and a central hyposignal suggesting intra-adenoma hemorrhage and then disappearance of the adenoma. Hydrocortisone was initiated in emergency to prevent any risk to life.

A case of male hypogonadism after Weil's syndrome is described. Hypogonadism was the result of complete hypothalamic-pituitary deficiency. The relationship between leptospirosis and the endocrinopathy, the incidence that leptospira attacks hypothalamic-pituitary axis, and the mechanism with which the microorganism may cause damage to the pituitary and/or the hypothalamus are discussed.

The majority of growth hormone deficient children (GHD) have a positive response to the acute administration of GRF. This suggests that their problem is an absence of the hypothalamic signal to release GH. A negative response to GRF suggests a pituitary deficiency, but chronic underestimulation of the pituitary might cause the poor response. To test this hypothesis, we administered GRF (20 ug/kg/day) during 7 days, to 5 prepubertal children with GHD (3 girls and 2 boys)with ages between 4, 9/12 and 12, 1/12 years. We performed 2 GRF tests (1 Ug/kg/iv)in these patients, one before GRF treatment and one after treatment. GH levels for each patient during both tests are shown in the table: We observed a positive response to GRF in 2 of 5 initially unresponsive children (40%) after chronic GRF treatment. We conclude that an initial negative response to GRF does not exclude an hypothalamic disorder, since repeated administration of GRF can stimulate the somatotropes to respond.

The clinical and endocrinological findings in 24 children with septo-optic dysplasia and/or agenesis of the corpus callosum are described with reference to posterior pituitary function in a report from the Institute of Child Health and The Hospital for Sick Children, London, UK.

Six patients with idiopathic isolated gonadotropin deficiency (IGD) were treated with 100 microgram LH-RH s.c. 3 times daily, leading to subnormal increases of serum gonadotropin (Gn) and testosterone (T) levels, and promoting puberty from stage I to stage II-III of TANNER. S.c. administration of 100 microgram of the more potent and longer-lasting analogue 6-D-Leu-10-Des-Gly-ethylamide-LH-RH induced LH and FSH rises after the very first application in these patients for more than 12 h. However, long-term therapy with the analogue (100 microgram s.c./day) did not improve hypogonadism. Paradoxically, on daily treatment (8 patients) with 6-D-Leu-10-Des-Gly-ethylamide-LH-RH the FSH serum levels fell after 1 week and the LH levels after 8 weeks of treatment.

We have observed the association of transient hypoglycemia, temporary ACTH deficiency, and elements of “maternal deprivation” or parental neglect in three children. Since reversible pituitary deficiency has been documented in the syndrome of “maternal deprivation” and since hypoglycemia can be the manifestation of ACTH and/or growth hormone deficiency, we suggest that recognition of hypoglycemia in the pediatric population may sometimes lead to the discovery of an adverse environment.

In a preceding communication (1) the diagnosis and therapy of combined androgenic deficiency and seminal inadequacy were considered. However, deficiencies in seminal function are observed commonly in males who present no evidences of androgenic failure or other sexual incompetency as evaluated by present diagnostic criteria. Moreover it is unlikely that pronounced grades of hypogonadotropic failure exist in these patients for, if that were true, androgenic deficiency states would likewise be noted. The consideration of seminal inadequacy alone, therefore, assumes definite clinical importance. Impairment of seminal function of the male, unaccompanied by androgenic failure, may be due to several factors: a) intrinsic testicular failure due to maldescent; b) extra-endocrine factors; c) altered metabolism due to thyroid disease; d) altered metabolism due to adrenal disease; e) inadequate gonadotropic activation of the germinal epithelium due to low-grade pituitary deficiency; and f) intrinsic germinal failure...

Except for unequivocal pituitary deficiency or abnormal sex chromosome patterns, the pathogenesis of testicular disorders is still relatively obscure. Advances in endocrinology are, however, clarifying the relationship of the gonadotropins to the development and regulation of testicular function. For some patients, particularly hypogonadotropic eunuchoids, this has opened the way to specific, if complex, therapy.

Following his defeat at Waterloo on June 18th, 1815, Napoleon returned to Paris. As he had come to dislike the Tuileries, which had no private gardens, he retired to the seclusion of the Elysee Palace, where he abdicated. He was joined by Hortense, ex-Queen of Holland, who was both his step-daughter, being a daughter of Josephine, and his sister-in-law, having been married to, but now separated from his brother, Louis Bonaparte. After days of vacillation, on June 25th, he secretly drove in a carriage, with blinds drawn, to Malmaison, eight miles from Paris, the home of his divorced wife Josephine, who had died about one year previously while he was in exile in the island of Elba. On his journey, he drove up the Avenue des Champs Elysees, crossed at the Etoile and turned on the rough patch of ground—stones, sand, and wild thickets—where they had begun to lay the foundations of the Arc de Triomphe. Some twenty-five years later, on December 15th, 1840, his coffin was borne triumphantly beneath this same arch on its way to the Invalides. Whilst at Malmaison, he decided to flee the country and, if possible, to escape to America. The French Provisional Government reluctantly agreed to place two ships, the Saale and the Meduse, then at anchor in the harbour of Rochefort, at his disposal.

Clinical studies of pituitary cachexia (Simmonds’ disease) (1) are fairly common. Calder (2) reviewed the literature up to 1932 and cited 70 cases. Since this time several new observations have been recorded. In no instance was reference made to a preceding acromegaly. Pituitary cachexia in its severest form denotes failure of the entire hypophyseal mechanism or at least complete failure of the anterior lobe. In 1928 Bailey and Cushing (3) described a syndrome termed ‘fugitive acromegaly’ in which the early evidences of acromegaly were replaced by a state of pituitary embarrassment. The terminal phenomenon, namely, cachexia, weakness, increased carbohydrate tolerance, etc., may well have been due to a failure of the acidophilic elements alone. Controlled clinical observations of such a selective pituitary deficiency are comparatively rare.

The diuretic action of extracts of the pituitary body was first described by Magnus and Schafer.1 Their finding has been confirmed repeatedly. Von den Velden2 showed that pituitrin may exert an opposite or antidiuretic effect. Reasoning that the polyuria of diabetes insipidus was caused by pituitary deficiency, he further used pituitary extracts successfully in the control of the polyuria. Recent papers by Smith and McClosky,3 Fromherz,4 and Stehle5 give a review of the literature. As yet there is no general agreement as to the explanation of the apparently contradictory results.The experiments reported in this paper were limited to a study of the action of pituitrin superimposed on a diuresis variously induced, and to a comparison of the effect of variation in dosage and method of administration. It was hoped that such experiments might throw some light on the question of the mechanisms responsible for the antagonistic actions reported. Rabbits anesthetized with morphine and urethane were used throughout...

Diversified types of eunuchoid patients were employed in this study in order to learn what influence the presence of testicular tissue had on effective doses of testosterone. Two patients were bilateral cryptorchids, 21 and 33 years of age, in whom no testicular tissue was demonstrable. Two others were 20 and 31 years of age and had undeveloped retractile testes which apparently were either nonfunctioning or which gave evidence of a minimal amount of activity. The fifth patient had had an unilateral orchipexy performed but was deficient in testicular function. The sixth patient exhibited definite hypogenitalism which was associated with a primary gonadotropic pituitary deficiency. Subcutaneous implants of testosterone as a method of treatment in cases of testicular deficiency were introduced experimentally by Deanesly and Parkes (1). Following this, reports of the clinical application of this method of therapy appeared in the literature (2). To be clinically expedient, a mode of therapy should be effectiv...

After diagnosis of non-functioning pituitary adenoma and impact assessment (pituitary deficiency, visual field disorder), the question of management arises between surgery and surveillance. This part of the Consensus document aims to clarify the principal situations encountered in clinical practice (visual disorder, pituitary deficiency, asymptomatic adenoma, etc.), so as to determine which ones indicate surgery and which ones simple surveillance. Particular contexts are also dealt with (elderly patients, young women hoping for pregnancy, etc). The principal surgical techniques (microscopy, endoscopy, etc.) are also considered. Finally, in case of surgery, the principal pathologic criteria are specified (immunolabeling, proliferation markers, etc.).

During the 16 years after a massive post-partum hemorrhage attended by coma, a patient had only occasional menses but went through three uneventful pregnancies. In the fourth month of her fourth pregnancy, there were both clinical and laboratory features of decreased thyroidal and adrenal function, which improved on hormonal replacement therapy. Tests done three months after delivery revealed decreased pituitary secretory capacity for ACTH, TSH and growth hormone. Although some pituitary-function tests may be contraindicated or unreliable in pregnancy, partial pituitary deficiency may be recognized and treated appropriately.

The answer to the question whether the genital atrophy, skeletal undergrowth, and excessive adiposity of the adiposogenital syndrome are due to a pituitary deficiency or to an injury of the hypothalamus without pituitary involvement has rested heretofore upon observation made in two closely allied ways, (1) the extent of the injury inflicted as determined at the time of operation, (2) the extent of the injury as determined by autopsy and a study of sections. Both of these methods are open to the objection that the most careful study may fail to reveal the extent of damage done.Another method is available for determining the significance of the pituitary and brain injury in the genesis of this syndrome, namely, that of a replacement therapy. If we have any confidence in the functional specificity of the endocrine glands, it follows that we must admit the significance of a pituitary impairment as the causative factor if the adiposogenital syndrome or any of its components can be corrected by pituitary admin...

Fifteen patients, 11 female and four male, with primary selective pituitary deficiency in gonadotropins were submitted to the subcutaneous administration of 100 to 400 mcg. of luteinizing hormone-releasing hormone (LH-RH). When compared to the effect of LH-RH in eight normal female subjects, two types of responses were observed: there were either small increments in both luteinizing hormone (LH) and follicle-stimulating hormone (FSH) or increases comparable to those observed in normal subjects. Five patients received 100 mcg. of LH-RH daily over four consecutive days. No additive nor depleting effects could be observed. The responses in seven patients given 400 mcg. were not significantly different from those obtained with 100 mcg. Our results indicate two possible etiologies of primary hypogonadotropic hypogonadism. A normal response in LH and FSH after administration of LH-RH assesses a selective hypothalamic deficit in releasing hormones, whereas a negative or low response suggests a dysfunction of the pituitary gonadotropic cell.

Insulin-induced hypoglycaemia was used to test pituitary function in six patients with suspected pituitary deficiency. In each, a fall in serum potassium concentration of from 0-63 to 1-48 mEq/litre (mean fall 1-10 mEq/litre +/- 0-30 SEM) was observed during the two hour period following administration of 1-15 units of insulin per kilogram body weight. In several patients the resulting hypokalaemia was at a level which has been associated with cardiac complications.

CLINICAL improvement in diabetes mellitus as a result of pituitary deficiency occurs uncommonly. It resembles the Houssay phenomenon produced experimentally in dogs.1 Only 14 cases had been reported up to the year of 1955, according to a review by Harvey and de Klerk.2 Since then, several other reports have appeared in the literature. The purpose of this communication is to present 3 additional cases and to review the recent literature. Case Reports Case 1. E.C., a 30-year-old married woman, gravida 4, para 1, was admitted to the Providence Lying-in Hospital on September 15, 1954, because of abdominal cramps and vaginal . . .

Using a sensitive radioimmunoassay, serum luteinizing hormone (LH) levels have been determined in 249 normal children (5 to 18 years of age), 30 normal adult males, 2 normal adult females throughout a menstrual cycle, and 19 patients with pituitary deficiency. The mean levels in prepubertal boys and girls were comparable (3.4 and 2.8 m.I.U. per milliliter, respectively) and began increasing at the same age (10 to 12 years) in both sexes. An increase in serum LH was noted in the males but not in the females before beginning sexual maturation was apparent clinically. In adult males and females, the mean serum LH levels (10.9 and 10.2 m.I.U. per milliliter, respectively) were approximately 3.5 times prepubertal values. Patients with pituitary deficiency had a very low mean level (1.7 m.I.U. per mililiter), but some immunochemical LH was found in all sera. In males, the urinary excretion of 17-ketosteroids had a statistically significant correlation (correlation coefficient=0.73) with the serum LH leterminations.