Hypothalamitis and pituitary atrophy.

Hypothalamitis is a rare inflammatory disorder involving the hypothalamus and classified as primary, or isolated, and secondary hypothalamitis. Secondary hypothalamitis although very rare is more common than the primary one and may occur in patients affected by autoimmune diseases such as autoimmune hypophysitis, systemic autoimmune diseases, infective diseases in patients affected by immune-deficit, paraneoplastic encephalitis, or in patients treated with immune checkpoint inhibitors. In accordance with the rarity of this disease, diagnosis and management of hypothalamitis prove to be challenging. The diagnosis requires a high index of clinical suspicion. The main symptoms may be: various degrees of hypopituitarism, neuropsychiatric and behavioral disorders, and disturbances of autonomic and metabolic regulation. Magnetic resonance images play a crucial role in the diagnosis of hypothalamitis and in the exclusion of a neoplastic lesion. Therapeutic management should be oriented according to the disease etiology. In most cases, after ruling out infective hypothalamitis, the mainstay of therapy consists of immunosuppressive treatment. Great attention should be paid to hormonal replacement therapy, if partial or total hypopituitarism is present, in particular in patients affected by diabetes insipidus, central hypoadrenalism and hypothyroidism. According to the complexity of this disease, a multidisciplinary approach is strongly advocated to reach an early diagnosis and an integrated therapy.

Pituitary society guidance: pituitary disease management and patient care recommendations during the COVID-19 pandemic-an international perspective.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the viral strain that has caused the coronavirus disease 2019 (COVID-19) pandemic, has presented healthcare systems around the world with an unprecedented challenge. In locations with significant rates of viral transmission, social distancing measures and enforced 'lockdowns' are the new 'norm' as governments try to prevent healthcare services from being overwhelmed. However, with these measures have come important challenges for the delivery of existing services for other diseases and conditions. The clinical care of patients with pituitary disorders typically involves a multidisciplinary team, working in concert to deliver timely, often complex, disease investigation and management, including pituitary surgery. COVID-19 has brought about major disruption to such services, limiting access to care and opportunities for testing (both laboratory and radiological), and dramatically reducing the ability to safely undertake transsphenoidal surgery. In the absence of clinical trials to guide management of patients with pituitary disease during the COVID-19 pandemic, herein the Professional Education Committee of the Pituitary Society proposes guidance for continued safe management and care of this population.

ENDOCRINOLOGY AND ADOLESCENCE: Dealing with transition in young patients with pituitary disorders.

INTRODUCTION: The transition age is the period between childhood to adulthood; it refers to a broad set of physical, cognitive and sociocultural modifications, arbitrarily defined as starting in late puberty and ending with full adult maturation. Pituitary disorders in adolescence represent a challenge that requires careful management during the transition to adult care. METHODS: Given the complexity of care of pituitary disorders in the transition age, we have reviewed the relevant medical literature focusing on aetiology, clinical manifestations, treatment strategies of GH deficiency (GHD), hypogonadotrophic hypogonadism (HH) in male and female adolescents, central hypothyroidism (CH), central adrenal insufficiency (CAI) and cranial diabetes insipidus (CDI) at this time. The objective of the present review is to provide an up-to-date evaluation of the transition period to evaluate the specific needs of adolescents with chronic pituitary disease in order to optimise their management. RESULTS: We provide an overview of current clinical management of GHD, HH, CH, CAI and CDI in the transition age. CONCLUSIONS: Specific changes occur in pituitary function during the transition period. A holistic approach including discussion of patients' concerns and emotional support should constitute a key component of managing pituitary disorders in adolescence. Special transition clinics where paediatric and adult endocrinologists work together, should be increasingly created and strengthened to bridge care, to promote continuity and adherence to treatment and to limit potential negative development, metabolic, skeletal and cardiovascular sequelae of discontinuity of care among adolescents with pituitary disorders.

Cystic tumors of the pituitary infundibulum: seminal autopsy specimens (1899 to 1904) that allowed clinical-pathological craniopharyngioma characterization.

A heterogeneous group of epithelial cystic tumors developed at the infundibulum and the third ventricle disconcerted pathologists at the dawn of the twentieth century. Very little was known at that time about the physiological role played by the pituitary gland, and there was almost complete ignorance regarding the function of the hypothalamus. Acromegaly, or enlargement of acral body parts, described in 1886 by Pierre Marie, was the only disease linked to primary hypertrophies of the pituitary gland, known as "pituitary strumas". A growing number of young patients manifesting an unexplained combination of physical and mental symptoms, including absent or delayed sexual maturation, progressive obesity, abnormal somnolence, and dementia-like changes in behavior were reported to present large solid-cystic tumors which characteristically expanded within the infundibulum and third ventricle, above an anatomically intact pituitary gland. Between 1899 and 1904, five seminal autopsy studies from different countries thoroughly described the anatomical relationships and histological features of this newly recognized type of infundibular tumors. These cases were instrumental in fostering the systematic investigation of similar lesions by the Austrian pathologist Jakob Erdheim (1874-1937), who in 1904 was able to classify these infundibulo-tuberal cysts under the common category of hypophyseal duct tumors. The pioneering American neurosurgeon Harvey Cushing (1869-1939) unsuccessfully attempted to surgically remove one of these cysts, for the first time in history, in 1902. The term "craniopharyngioma", chosen by Cushing in 1929 to designate these lesions, would eventually prevail over Erdheim's more accurate denomination, which linked their origin to squamous cell remnants derived from the embryological structures that give rise to the pituitary gland. This paper presents a comprehensive, renewed account of the five clinical-pathological reports which laid the groundwork for the proper clinical diagnosis, topographic conceptualization and pathological categorization of craniopharyngiomas.

Hypothalamic-pituitary sarcoidosis with vision loss and hypopituitarism: case series and literature review.

PURPOSE: Hypothalamic-pituitary (HP) neurosarcoidosis (NS) accounts for 0.5 % cases of sarcoidosis and 1 % of HP masses. Correlative data on endocrine and neurological outcomes is lacking. METHODS: Retrospective case series and literature review of presentation, treatment and outcome of HP NS. RESULTS: Our series includes 4 men, ages 34-59, followed for a median of 7.3 years (range 1.5-17). All had optic neuropathy, multiple pituitary hormone abnormalities (PHAs) and other organ involvement by sarcoidosis (lung, sino-nasal, brain/spine and facial nerve). Two patients had central diabetes insipidus and one impaired thirst with polydipsia. After treatment with high-dose glucocorticoids, optic neuropathy improved in one case and stabilized in the others. After treatment, HP lesions improved radiologically, but PHAs persisted in all cases. Review of four published series on HP NS in addition to ours yielded 46 patients, age 37 ± 11.8 years, 65 % male. PHAs consisted of anterior hypopituitarism (LH/FSH 88.8 %, TSH 67.4 %, GH 50.0 %, ACTH 48.8 %), hyperprolactinemia (48.8 %) and diabetes insipidus (65.2 %). PHAs were the first sign of disease in 54.3 % patients. Vision problems occurred in 28.3 % patients, but optic neuropathy was not well documented in previous series. Most patients (93.5 %) received high-dose glucocorticoids followed by taper; 50 % also received other immunomodulators, including methotrexate, mycophenolate mofetil, cyclosporine, azathioprine, infliximab and hydrochloroquine. Only 13 % patients showed improvement in PHAs. All-cause mortality was 8.7 %. CONCLUSION: HP NS is a serious disease requiring multidisciplinary treatment and lifelong follow-up. Prospective multicentric studies are needed to determine a more standardized approach to HP NS and outline predictors of disease outcome.

Pituitary centers of excellence.

Pituitary tumors and associated neuroendocrine disorders pose significant challenges in diagnostic and therapeutic management. Optimal care of the "pituitary patient" is best provided in a multidisciplinary collaborative environment that includes not only experienced pituitary practitioners in neurosurgery and endocrinology, but also in otorhinolaryngological surgery, radiation oncology, medical oncology, neuro-ophthalmology, diagnostic and interventional neuroradiology, and neuropathology. We provide the background and rationale for recognizing pituitary centers of excellence and suggest a voluntary verification process, similar to that used by the American College of Surgeons for Trauma Center verification. We propose that pituitary centers of excellence should fulfill 3 key missions: (1) provide comprehensive care and support to patients with pituitary disorders; (2) provide residency training, fellowship training, and/or continuing medical education in the management of pituitary and neuroendocrine disease; and (3) contribute to research in pituitary disorders. As this is a preliminary proposal, we recognize several issues that warrant further consideration including center and surgeon practice volume as well as oversight of the verification process.

[Diagnosis and treatment of patients with primary "empty" sella turcica syndrome at the stage of sanatorium-and-spa rehabilitation].

The authors report the first attempt to develop the treatment strategy for patients with primary "empty" sella turcica syndrome based at a health resort facility. It is shown that combined therapy including radon baths and acupuncture at specific auricular points makes it possible to improve functioning of the pituitary-ovarian system, decrease body weight, normalize blood prolactin level, eliminate visceral obesity, enhance tissue sensitivity to insulin, reduce hyperinsulimenia and fertility problems (anovulation, hyperandrogenism, and hypoluteinism) associated with insulin resistance.

Diagnosis of secondary adrenal insufficiency in patients with hypothalamic-pituitary disease: comparison between serum and salivary cortisol during the high-dose short synacthen test.

OBJECTIVE: Accurate assessment of adrenal function is essential in patients with hypothalamic-pituitary-adrenal (HPA) disease. The measurement of salivary cortisol (SaC) instead of serum cortisol (SeC) offers several advantages, such as the determination of the free hormone. We evaluated the diagnostic value of SeC and SaC both unstimulated and during a high-dose short synacthen test (HDT) in comparison to the insulin tolerance test (ITT). DESIGN: Comparative study between 2005 and 2007. METHODS: Fifty-five patients with HPA impairment and 21 healthy controls were enrolled. Samples were collected in the early morning and over 120 min during the HDT. Receiver operating characteristic analysis revealed individual thresholds for four HDT periods (0-30, 0-60, 0-90, and 0-120 min). RESULTS: The ITT identified 30 subjects as adrenal insufficient. With respect to the four HDT periods, sensitivity and specificity were 67-79% and 71-88% for SeC, compared with 63-72% and 72-86% for SaC. If upper and lower thresholds (with specificities >95%) were applied, patients were diagnosed in 40-45% by SeC and in 25-31% by SaC. The combination of basal cortisol and HDT allowed a diagnosis in 47-49% (SeC) and in 42-45% (SaC) respectively. CONCLUSION: We suggest the determination of basal SeC or SaC as first-line test. In comparison to the ITT, the HDT has only limited value in screening for alterations of the HPA axis. If the HDT is performed, sampling may be limited to 30 min post-synacthen, using either SeC or SaC. Due to the ease of collection and the independence of binding proteins, SaC may be preferable.

Treating primary infertility due to pituitary atrophy with Chinese herbs: a case report.

In the report a patient who suffered from secondary amenorrhea for 6 years and primary infertility for 2 years due to pituitary atrophy was successfully cured with Chinese herbs. After orally administered Chinese herbs for 1 month, the patient menstruated once and became pregnant later.

Imaging of sellar and parasellar lesions.

The sellar and parasellar region is an anatomically complex area where a number of neoplastic, infectious, inflammatory, developmental and vascular pathologies can occur. Differentiation among various etiologies may not always be easy, since many of these lesions may mimic the clinical, endocrinologic and radiologic presentations of pituitary adenomas. The diagnosis of sellar lesions involves a multidisciplinary effort, and detailed endocrinologic, ophthalmologic and neurologic testing are essential. CT and, mainly, MRI are the imaging modalities to study and characterise normal anatomy and the majority of pathologic processes in this region. We here provide an overview of the most relevant MRI and CT characteristics together with clinical findings of pituitary tumors, vascular, inflammatory and infectious lesions found in the sellar/parasellar region in order to propose an appropriate differential diagnosis.

El eje hipotálamo-hipófisis en el niño: consideraciones de imagen / The hypothalamus-hypophysis axis in the child: imaging considerations

Este trabajo aborda una revisión general con resonancia magnética (RM) de los aspectos anatómicos del eje hipotálamo-hipofisario en el grupo pediátrico y de sus alteraciones estructurales. El mayor rendimiento diagnóstico se ha producido en el hipopituitarismo congénito, que frecuentemente se expresa en el niño por un déficit de hormona del crecimiento, al mejorar la delimitación del complejo malformativo de la línea media. La ausencia de visualización total o parcial del tallo hipofisario y la presencia de una neurohipófisis ectópica han cambiado el concepto clásico del enanismo hipofisario idiopático, y han acotado un grupo de pacientes con esta alteración estructural que muestran una mayor resistencia al tratamiento con hormona y una frecuente aparición evolutiva de otras deficiencias adenohipofisarias. La demostración de una hipoplasia aislada de la adenohipófisis puede orientar el diagnóstico de un hipopituitarismo de origen genético. Los tumores de la región supraselar y de la región posterior del tercer ventrículo, craneofaringiomas, gliomas y germinomas, son la causa más frecuente de disfunción endocrina adquirida, aunque ésta suele aparecer como resultado de las actuaciones terapéuticas sobre aquellos. Los adenomas hipofisarios son tumores poco frecuentes en el niño y predominan los microadenomas en esta edad. La histiocitosis de células de Langerhans se muestra como un aumento de grosor y captación del tallo hipofisario y su diagnóstico se apoya en las manifestaciones asociadas en otros órganos; en ausencia de éstas, el diagnóstico diferencial más importante de estos hallazgos es el germinoma. El estudio radiológico del eje hipotálamo-hipófisis debe incluir imágenes con contraste y extenderse al resto del sistema nervioso central en función de la información clínica aportada

This paper provides a general review with MRI of anatomical aspects of the hypothalamus-hypophysis axis in the pediatric group and of its structural alterations. The greatest diagnostic yield has been found in congenital hypopituitarism, frequently expressed in the child by growth hormone deficit, through an improvement of the delimitation of the malformative complex of the middle line. Absence of total or partial visualization of the pituitary stem and the presence of ectopic neurohypophysis have changed the classical concept of idiopathic pituitary dwarfism, delimiting a group of patients with this structural alteration that show greater resistance to hormone treatment and frequent evolutive appearance of other adenopituitary deficiencies. Demonstration of an isolated hypoplasia of the adenopituitary may orient the diagnosis of a hypopituitarism of genetic origin. The tumors of the suprasellar regional and the posterior region of the III ventricle, craniopharyngioma, gliomas and germinomas are the most frequent cause of acquired endocrine dysfunction, although this generally appears as a result of the therapeutic actions on them. Hypopituitary adenomas are rare tumors in the child and microadenomas predominate at this age. Langerhan cell histiocytosis is shown as an increase in thickness and uptake of the pituitary stem and its diagnosis is supported by the associated manifestations in other organs. In absence of these, the most important differential diagnosis of these findings is the germinoma. The radiology study of the hypothalamus-hypophysis axis should include images with contrast and extend to the rest of the central nervous system based on the clinical information supplied

Langerhans cell histiocytosis limited to the pituitary-hypothalamic axis--two case reports.

Langerhans cell histiocytosis rarely presents as a solitary lesion in the pituitary-hypothalamic region, and is indistinguishable from germinoma, which occurs much more frequently, especially in Japanese. A 14-year-old girl and a 9-year-old girl presented with polydipsia and polyuria as the initial symptoms. Magnetic resonance (MR) imaging demonstrated a round mass at the pituitary stalk appearing as isointense on T1-weighted imaging and hyperintense on T2-weighted imaging. Endocrinological examination revealed mild hypopituitarism with central diabetes insipidus. Both patients underwent open craniotomy. Histological examination revealed granulomatous tissue with eosinophil infiltration and frequent Langerhans histiocyte clustering, compatible with the diagnosis of Langerhans cell histiocytosis. Low-dose local irradiation of 20 Gy was administered. First patient was followed up for 8 years, and her hypopituitarism gradually improved to a minimal level with only amenorrhea as the residual symptom. Recent MR imaging showed no residual mass at the region. Second patient was followed up for 15 months, and her diabetes insipidus is stable. MR imaging performed 5 months after the treatment showed marked reduction of the mass. These cases reemphasize the importance of histological diagnosis for lesions with similar neuroimaging appearances. Biopsy and low-dose irradiation are an effective treatment for this rare and essentially benign lesion, as opposed to attempting total removal of the mass.

A review of endocrine changes in anorexia nervosa.

Anorexia nervosa is a syndrome of unknown etiology. It is associated with multiple endocrine abnormalities. Hypothalamic monoamines (especially serotonin), neuropeptides (especially neuropeptide Y and cholecystokinin) and leptin are involved in the regulation of human appetite, and in several ways they are changed in anorexia nervosa. However, it remains to be clarified whether the altered appetite regulation is secondary or etiologic. Increased secretion of corticotropin-releasing hormone and proopiomelanocortin seems to be secondary to starvation, however, there is evidence that it may maintain and intensify anorexia, excessive physical activity and amenorrhea. Hypothalamic amenorrhea, which is a diagnostic criterion in anorexia nervosa, is not solely related to the low body weight and exercise. Growth hormone resistance with low production of insulin-like growth factor I and high growth hormone secretion reflect the nutritional deprivation. The nutritional therapy of patients with anorexia nervosa might be improved by administering an anabolic agent such as growth hormone or insulin-like growth factor I. So far none of the endocrine abnormalities have proved to be primary, however, there is increasing evidence that some of these might participate in a vicious circle.

Imaging of the pituitary in children with growth disorders.

Magnetic resonance imaging reveals the anatomy of the pituitary and hypothalamus with unique detail. The clinical and biochemical investigation of short stature in childhood may be difficult and complex; magnetic resonance imaging of the pituitary is a non-invasive technique which can help to clarify the diagnosis of growth hormone insufficiency and to determine its cause. Most cases of growth hormone insufficiency have previously been considered to be idiopathic; in about 60% of these children, magnetic resonance imaging shows a characteristic structural abnormality which has been termed pituitary stalk interruption syndrome. The most important role of magnetic resonance imaging is in the diagnosis of destructive lesions of the hypothalamic-pituitary axis which may initially present with growth failure.

Current concepts of imaging in patients with pituitary/hypothalamic dysfunction.

MRI has value in differentiating the normal anatomy and abnormalities of the hypothalamic and pituitary regions. The hypothalamus and the pituitary gland are contiguous structures. They are functionally and physiologically inseparable. The hypothalamus functions primarily as an integrating mechanism for various autonomic and neuroendocrine activities, including temperature regulation, water balance, behavior, and appetite. The adenohypophysis of the pituitary gland contains at least five histologically distinct cell types responsible for hormonal secretion. The characteristic locations of these functional cell types correlate well with the common sites of various pituitary adenomas. MRI can visualize the pituitary gland and the hypothalamus noninvasively in healthy people and in patients with diverse diseases.

MR imaging of pituitary region lesions with gadodiamide injection.

Twelve patients with known or suspected pituitary lesions underwent MR imaging with gadodiamide injection at a dose of 0.1 (n = 5) or 0.3 (n = 7) mM/kg. Six of the patients were also studied with 0.1 mM/kg gadopentetate dimeglumine. Consistent with previous reports gadodiamide injection was found to be a safe and effective contrast medium for MR imaging of the pituitary region. No additional diagnostic information was obtained using 0.3 mM/kg gadodiamide injection compared to 0.1 mM/kg gadopentate dimeglumine in the same patients. The high dose (0.3 mM/kg) gadodiamide injection in 7 patients did not shorten the T2 value sufficiently to overwhelm the T1 shortening and leave pathologic lesions hypointense compared to precontrast studies. With the comparable relaxivities of gadodiamide injection and gadopentetate dimeglumine, similarities in results have to be expected when using these media for MR image enhancement.

Hypothalamic and pituitary pathology.

This article details the intricate anatomy and elegant physiology of the hypothalamic-pituitary axis. The discussion is meant to confer an understanding of the principles of neuroendocrinology appropriate for the radiologist interpreting imaging studies of this region. The clinical presentations of the diseases that occur in this area of the central nervous system are unique and therefore are discussed in some detail. The radiologic features of the diseases affecting the hypothalamic-pituitary axis are described and correlated with the relevant pathology.