Hypothalamic-pituitary Region Research Articles

Pituitary stalk thickening on MRI: when is the best time to re-scan and how long should we continue re-scanning for?

Magnetic resonance imaging (MRI) has proved to be an essential tool in the assessment of pituitary stalk lesions including lymphocytic infundibulo-hypophysitis, Langerhans cell histiocytosis (LCH), germ cell tumours, nongerminomatous germ cell tumours, pituicytomas and other tumours, metastases from lymphoma or breast cancer, Wegener's hypophysitis, neurosarcoidosis and inflammatory infiltrations by infectious diseases. The diagnosis of lesions determining pituitary stalk thickness is challenging, and the identification of the underlying condition may require a long-term follow-up. Thus, clinicians should readily recognize that, when the diagnosis of central diabetes insipidus has been established, specific MRI sequences should be used in the assessment of the hypothalamic-pituitary region, and whole-brain evaluation is recommended. For clinical practice, a timely diagnosis is advisable to avoid central nervous system damage, pituitary defects and the risk of dissemination of germ cell tumours or organ involvement by LCH. Proper aetiological diagnosis can be achieved via a series of steps that start with careful observation of several neuroimaging predictors and endocrine dysfunction and then progress to more sophisticated and advanced imaging techniques.

Severe growth hormone deficiency and empty sella in obesity: a cross-sectional study.

Obesity is associated with blunted growth hormone (GH) secretion. In some individuals, hypothalamic-pituitary (HP) structural lesions may contribute to GH deficiency (GHD). We explored pituitary morphology in obese patients with suspected GHD and its association with cardiovascular risk factors, body composition, and cardiac morphology. One hundred and eighty-four adults obese patients with symptoms and signs of GHD (147 females and 37 males; mean age 46.31 ± 12.11 years), out of 906 consecutive white obese outpatients, were evaluated. The main measures were anthropometric data, blood pressure, lipid profile, glycemic parameters, pituitary hormones, and insulin-like growth factor-1 values, echocardiography, magnetic resonance imaging (MRI) of the HP region, body composition, and growth hormone-releasing hormone plus arginine test. Seventy patients had GHD (GH peak values <4.2 μg/mL). GHD patients showed significantly higher body mass index and fat mass, lower lumbar bone mineral density, increased left ventricular mass index, and epicardial fat thickness. The MRI of the HP region showed empty sella (ES) in 69 and normal pituitary in one of the 70 GHD patients; the 114 patients with normal GH response had ES (n = 62, 54 %), normal pituitary (n = 37, 32 %), microadenomas (n = 10, 8 %), and other pituitary abnormalities (n = 5, 4 %). ES was a significant independent predictor of GH secretory capacity as determined by multiple regression analysis. The close relationship between ES and GH secretory capacity points out to the possibility of the organic nature of GHD in a portion of obese individuals and opens a new scenario with regard to the potential of GH treatment on metabolic consequences of obesity.

Pituitary dysfunction in adult patients after cranial irradiation for head and nasopharyngeal tumours

BackgroundPituitary insufficiency after radiotherapy in the hypothalamic pituitary region is a well-known complication. However, endocrine assessments are not incorporated in the follow-up after cranial irradiation for head and neck tumours. Aim of the studyTo evaluate pituitary function in patients cranially irradiated for non-pituitary tumours. Patients and methodsEvaluation of pituitary function in all available patients treated at our centre with cranial radiotherapy for head and neck tumours. ResultsWe included 80 patients. Forty patients were treated for cerebral tumours, 15 for nasopharyngeal tumours, and 25 for different tumours like meningioma or cerebral metastasis. Mean age was 47.5 (18.6–89.7)years. Mean radiation dose delivered at the pituitary region was 56.27Gy (40.0–70.0). Pituitary insufficiency was present in 16 patients within 2years after irradiation 23/49 patients (47%) after 5years and 27/45 (60%) after 10years and 31/35 patients (89%) after 15years. ConclusionPituitary insufficiency is highly prevalent in adult patients treated with cranial radiotherapy for head and nasopharyngeal tumours. These prevalence rates are comparable to those observed after radiotherapy for pituitary tumours. Because hormone replacement of endocrine deficits improves quality of life and prevents potential severe complications, such as Addisonian crises, periodical evaluation of pituitary function is advocated.

High prevalence of early hypothalamic-pituitary damage in childhood brain tumor survivors: need for standardized follow-up programs.

Childhood brain tumor survivors (CBTS) are at increased risk to develop endocrine disorders. Alerted by two cases who experienced delay in diagnosis of endocrine deficiencies within the first 5 years after brain tumor diagnosis, our aim was to investigate the current screening strategy and the prevalence of endocrine disorders in survivors of a childhood brain tumor outside of the hypothalamic-pituitary region, within the first 5 years after diagnosis. Firstly, we performed a retrospective study of 47 CBTS treated in our center, diagnosed between 2008 and 2012. Secondly, the literature was reviewed for the prevalence of endocrine disorders in CBTS within the first 5 years after diagnosis. Of 47 CBTS eligible for evaluation, in 34% no endocrine parameters had been documented at all during follow up. In the other 66%, endocrine parameters had been inconsistently checked, with different parameters at different time intervals. In 19% of patients an endocrine disorder was found. At literature review 22 studies were identified. The most common reported endocrine disorder within the first 5 years after diagnosis was growth hormone deficiency (13-100%), followed by primary gonadal dysfunction (0-91%) central hypothyroidism (0-67%) and primary/subclinical hypothyroidism (range 0-64%). Endocrine disorders are frequently seen within the first 5 years after diagnosis of a childhood brain tumor outside of the hypothalamic-pituitary region. Inconsistent endocrine follow up leads to unnecessary delay in diagnosis and treatment. Endocrine care for this specific population should be improved and standardized. Therefore, high-quality studies and evidence based guidelines are warranted.

Burkitt's lymphoma presenting with hypopituitarism: a case report and review of literature.

SummaryHypopituitarism is a rare presentation of Burkitt's lymphoma (BL). The purpose of this report is to present a case of BL presenting with panhypopituitarism and to review other case reports of lymphoma presenting with pituitary dysfunction to highlight the distinguishing features of these cases from other benign aetiologies of pituitary dysfunction such as non-functioning pituitary adenomas. We reviewed a total of 11 cases of lymphoma presenting with pituitary dysfunction published from 1998 to 2013 including the present case. The demographics, clinical presentations, laboratory features, radiological findings, histological diagnosis, treatment administered and outcomes were described. Of the total number of patients, 45.5% of the cases had diffuse large B-cell lymphoma while 27.3% had BL. Anterior pituitary dysfunction was more common than posterior pituitary dysfunction at presentation. The other common associated presenting symptoms were painful ophthalmoplegia, cranial nerve palsies and constitutional symptoms. Hypothalamic–pituitary abnormalities were often demonstrated radiologically to be associated with cavernous sinus and/or stalk involvement. All patients who completed immunochemotherapy responded haematologically. Pituitary dysfunction also improved in most cases although the recovery tended to be partial. In conclusion, a high index of suspicion of underlying malignancy, such as lymphoma, should be present in patients presenting with acute pituitary dysfunction associated with painful ophthalmoplegia, rapidly evolving neurological features, radiological features atypical of a pituitary adenoma and constitutional symptoms. An early diagnosis is essential as prompt initiation of definitive therapy will induce disease remission and recovery of pituitary dysfunction.Learning points Hypopituitarism may be the presenting symptom of lymphoma in the absence of associated overt symptoms or signs of a haematological malignancy resulting in delay in diagnosis and institution of treatment.Pituitary dysfunction due to tumour infiltration has a greater tendency to involve the posterior pituitary and infundibulum resulting in diabetes insipidus and hyperprolactinaemia compared with a non-functioning pituitary adenoma.The common associated symptoms of hypopituitarism due to lymphoma infiltration of the hypothalamic–pituitary system include painful ophthalmoplegia, cranial nerve palsies and constitutional symptoms.Radiological abnormalities of the hypothalamic–pituitary region are usually present and often associated with cavernous sinus or stalk involvement.With early institution of definitive treatment, both haematological response and improvement of pituitary dysfunction are expected although the reversal of hypopituitarism tends to be partial and delayed.A high index of suspicion of underlying malignancy such as lymphoma should be present in patients presenting with acute pituitary dysfunction associated with painful ophthalmoplegia, radiological features atypical of pituitary adenomas and constitutional symptoms to enable early diagnosis and prompt initiation of definitive therapy.

Russian registry of patients with tumors of the hypothalamic-pituitary region (OGGO): October 2013 update for acromegaly

The Russian Registry of patients with tumors of the hypothalamic–pituitary region (OGGO) is a national registry founded in 2004 by Russian society for Endocrinology and Endocrinology Research Centre as a patient registry for acromegaly, in 2006 it was expanded to collect information on all lesions of the hypothalamic–pituitary region, in 2010 the first fully electronic version and in 2013 a new upgraded electronic online version were implemented. At this point the Registry is actively supported by 22 out of 83 regions of Russia, representing about 1/3 of population.

Comment on: Double, Synchronous Pituitary Adenomas Causing Acromegaly and Cushing’s Disease. A Case Report and Review of Literature. Endocr Pathol 2013;24:92–99

To the Editor: We read with great interest the recent paper by Zielinski et al. entitled “Double, Synchronous Pituitary Adenomas Causing Acromegaly and Cushing’s Disease. A Case Report and Review of Literature” published in Endocrine Pathology, in which the authors reported a rare case of a 47-year-old man with double clinically active pituitary adenomas causing simultaneous occurrence of signs and symptoms of acromegaly and Cushing’s disease and reviewed the literature regarding multiple pituitary adenomas [1]. In a manuscript with Review of the literature published in Magnetic Resonance Imaging [2], we reported the simultaneous occurrence of multiple non-functioning pituitary microadenomas, the first case with three coexisting tumors diagnosed in vivo up to that time, in a 37-year-old woman who was referred to our outpatient clinic reporting oligomenorrhea, significant weight gain, and persistent frontal and retroocular headache for several years. Physical examination showed moderate hirsutism and “moon face” while both basal and dynamic endocrine evaluation showed the presence of normal hypothalamic pituitary function. Magnetic resonance imaging (MRI) of hypothalamic-pituitary region revealed an enlarged sella turcica occupied by three distinct hypointense areas measuring less than 5 mm in diameter in the left, medial, and right sides of the pituitary, respectively. This finding was confirmed, 6 months later, by a second MRI that also showed a slight increase in dimensions of microadenomas. In the case report by Zielinski et al., basal and dynamic endocrine evaluation confirmed the diagnosis of active acromegaly also revealing a condition of pituitary-dependent hypercortisolism. Preoperative MRI showed a slightly enlarged and asymmetrical pituitary characterized by the presence of two separated intrasellar microadenomas with different intensity. The patient underwent transsphenoidal neurosurgery and the presence of two distinct, separated masses was confirmed. Also in our case, omitted as a reference in the article by Zielinski et al., the preoperative MRI suggestion of three different and well-defined adenomas was confirmed by transsphenoidal surgery. The occurrence of multiple pituitary adenomas is considered as one of the strongest confirmations regarding the role of abnormal extrapituitary regulatory mechanisms in the pathogenesis of pituitary tumors [3]. The coexistence of multiple adenomas in the pituitary gland of the same patient supports the pathogenic role of abnormal stimulatory and/or inhibitory extrahypophiseal factors which are able to promote growth and clonal expansion of genetically altered cells also potentially playing a role in the recurrence of pituitary tumors [4]. In conclusion, the coexistence of two or more adenomas in a single pituitary gland is a rarely reported clinical event and a very infrequent surgical entity, but already in 1999 we described the first case of simultaneous occurrence of triple nonfunctioning pituitary adenomas diagnosed in vivo, whereMRI allowed preoperative identification.

Pineal region tumors: Clinical symptoms and syndromes

The present paper investigates the clinical picture and the different clinical signs that reveal pineal region tumors or appear during the course of the follow-up. Biological malignancy and tumor extension determine the semiology and its setting up mode. Typical endocrine signs, dominated by abnormal puberty development, are frequently a part of the clinical scene. Bifocal or ectopic localization in the hypothalamic-pituitary region is accompanied by other endocrine signs such as ante- or post-pituitary insufficiencies which occur several months or even years after the first neurological signs appear. Due to a mass syndrome and obstructive hydrocephalus, intracranial hypertension signs are frequent but unspecific. A careful ophthalmologic examination is essential to search upward gaze paralysis and other signs of the Parinaud's tetrad or pentad. Midbrain dysfunction, including extrinsic aqueduct stenosis, are also prevalent. Except for abnormal pubertal signs, hyper-melatoninemia (secretory tumors) or a-hypo-melatoninemia (tumors destructing pineal) generally remains dormant. Some patients present sleep problems such as narcolepsy or sleepiness during the daytime as well as behavioral problems. This suggests a hypothalamic extension rather than a true consequence of melatonin secretion anomalies. Similarly, some patients may present signs of a “pinealectomized” syndrome, including (cluster) headaches, tiredness, eventually responsive to melatonin.

Hyperprolactinemia in polycystic ovary syndrome

Mild hyperprolactinemia is present in polycystic ovary syndrome (PCOS) with a frequency of 20 – 30%. There is a controversy whether they have common mechanisms or are only coincidental. Some characteristic hormonal disturbances of PCOS can promote themselves the hypersecretion of PRL, primarily the persistent and unopposed estrogen secretion, a consequence of the frequent anovulation. We studied retrospectively the data of 123 PCOS-patients hospitalized in Endocrinology Clinic Târgu Mures between 2005 – 2008. The diagnosis was based on the Rotterdam consensus criteria (2003), but including the cases with hyperprolactinemia and hypothyroidism, too. About one third of the patients had hyperprolactinemia including 15 cases of microprolactinomas (12% of all patients). Among hyperprolactinemics 61% had microprolactinomas – in presence of different other hyperprolactinemia inducing factors, while only 15% – in absence of these. The incidence of microprolactinomas was 10 times higher in PCOS group having hyperprolactinemic factors compared to the group without such a factors (p < 0.0001). Most frequent hyperprolactinemia inducing factors were: oral contraceptives with estrogenic component, antidopaminergic medicines, as neuroleptics (clorpromazine, clozapine) and metoclopramide, while from associated endocrinopathies hypothyroidism and hyperestrogenism. Taking into account the incidence of microprolactinomas (12%), we consider necessary the imagistic investigation of the hypothalamic-pituitary region at patients having PCOS with evident hyperprolactinemia. At hyperprolactinemic patients must be avoided all the hyperprolactinemia inducing factors, and the hyperprolactinemic states, including microprolactinomas must be treated correctly and in time.

Сравнительная характеристика нарушений физического и полового развития у детей и подростков (мальчиков) с различными объемными образованиями гипоталамо-гипофизарной области

В данной статье авторы анализируют результаты обследования 29 мальчиков-подростков с различными объемными образованиями гипоталамо-гипофизарной области. Установлено разно-образие нарушений роста и развития, таких как задержка роста (20,6 %), задержка роста и пубертата (20,6 %), истинное преждевременное половое развитие (13,8 %) и др. Наиболее часто встречались пациенты с неактивной аденомой гипофиза — 11 случаев из 29 (37,9 %). Наиболее часто задержка физического и полового развития наблюдалась у больных с неактивной аденомой гипофиза — в 6 случаях (20,6 %).

Isolated tumorous Langerhans cell histiocytosis of the brainstem: a diagnostic and therapeutic challenge

Langerhans cell histiocytosis (LCH) of the CNS is a rare entity, known to involve primarily the hypothalamicpituitary region, with the clinical hallmark of diabetes insipidus. There have been a few reports of CNS LCH involving the brainstem as intraparenchymal enhancing lesions, but this has never been the presenting complaint of LCH. The authors report on a 7-year-old boy who presented with right cerebellopontine syndrome, in whom a well-defined, solid, enhancing lesion in the brainstem was diagnosed. Clinicoradiological differential diagnosis included glioma and tuberculosis. Biopsy revealed atypical histiocytes positive for CD68, CD1a, and S100 protein; these are the diagnostic features of LCH on histopathological examination. The rapid growth of the lesion was controlled with a chemotherapeutic regimen of cladribine.

How to approach endocrine assessment in severe obesity?

The increasing numbers of severely obese patients (body mass index BMI >40 kg/m(2) ) represent a significant management challenge. These patients are at risk of obesity-related complications that may be driven by changes in endocrine function. Their care may potentially be complex at times, and therefore, an appropriate assessment strategy will be relevant to timely diagnosis and management. In this article, we discuss an approach to the endocrine assessment of the severely obese patient. We consider the clinical question in three categories that may also represent different complexities in terms of subsequent management: (i) obesity as a consequence of structural lesions at the hypothalamic-pituitary region; (ii) obesity as a consequence of inherited and genetic syndromes; and (iii) functional neuroendocrine hormone abnormalities relating to obesity. The first two categories are associated with hypothalamic dysfunction, of which hypothalamic obesity is a consequence. Additionally, the implications and difficulties associated with imaging severely obese patients are discussed from an endocrinological perspective and we provide practical guidance on which to base practice.

Approach to the Patient With Hypogonadotropic Hypogonadism

Hypogonadotropic hypogonadism (HH) or secondary hypogonadism is defined as a clinical syndrome that results from gonadal failure due to abnormal pituitary gonadotropin levels. HH may result from either absent or inadequate hypothalamic GnRH secretion or failure of pituitary gonadotropin secretion. Several congenital and acquired causes, including functional and organic forms, have been associated with this condition. One important aspect of the HH diagnosis is that it may reflect the presence of a tumor of the hypothalamic pituitary region or even a systemic disease. On the other hand, functional forms of HH, characterized by a transient defect in GnRH secretion, are relatively common in women, in response to significant weight loss, exercise, or stress leading to hypothalamic amenorrhea. HH is typically characterized by low circulating sexual steroids associated with low or inappropriately normal gonadotropin levels. The precise and early diagnosis of HH can prevent negative physical and psychological sequelae, preserve normal peak bone mass, and restore the fertility in affected patients.

GH dynamics in oral glucose tolerance test in children and adolescents with tall stature

Conclusions Assessment of GH dynamics in OGTT in children and adolescents with tall stature in various stages of pubertal development for documenting a possible autonomous GH secretion. Our study included 44 subjects, 18 girls and 26 boys, aged between 6.5 years and 17.3 years diagnosed with constitutional tall stature. • The inclusion criterion was height ≥+2 DS. • The exclusion criteria were: diabetes, thyroid dysfunction, Cushing's syndrome, hypothalamicpituitary pathology, renal failure, medication that alters glucose/ GH dynamics such as estrogen and thyroid hormones. • The following parameters were assesed: historical and auxological data, clinical examination, laboratory evaluations: karyotype, thyroid function, androgens, IGF1 (CLIA method with detection limit 3-1500ng/ml), IGFBP3, prolactin, evaluation of other pituitary hormone deficiency, bone age, cardiac ultrasound, eye examination, CT/MRI of the hypothalamic-pituitary region. OGTT was performed with 1.75 g/kg of glucose po. Glucose and GH (CLIA method with detection limit 0,1-80 ng/ml) were tested at 0, 30, 60, 90 and 120 minutes. • Brain imaging was performed in 20 cases. • Statistical analysis was performed using PASW software version 18, 2010 using Pearson correlation, T test, and Mann-Whitney test and the level of significance used was p 1ng/ml. • For girls GH nadir was higher than for boys. • The lowest value of GH both for girls and boys was at 90 minutes. • 2 patients with IGF1>+2DS for chronological age had normal levels of IGFBP3. • In 6 patients with GH suppression >1ng/ml, the levels of IGF1 and IGFBP3 were normal. • CT/MRI of the hypothalamic-pituitary region revealed an inhomogeneous pituitary gland. P 805

Hippocampal volumes in patients exposed to low-dose radiation to the basal brain. A case–control study in long-term survivors from cancer in the head and neck region

BackgroundAn earlier study from our group of long time survivors of head and neck cancer who had received a low radiation dose to the hypothalamic-pituitary region, with no signs of recurrence or pituitary dysfunction, had their quality of life (QoL) compromised as compared with matched healthy controls. Hippocampal changes have been shown to accompany several psychiatric conditions and the aim of the present study was to test whether the patients’ lowered QoL was coupled to a reduction in hippocampal volume.MethodsPatients (11 men and 4 women, age 31–65) treated for head and neck cancer 4–10 years earlier and with no sign of recurrence or pituitary dysfunction, and 15 matched controls were included. The estimated radiation doses to the basal brain including the hippocampus (1.5 – 9.3 Gy) had been calculated in the earlier study. The hippocampal volumetry was done on coronal sections from a 1.5 T MRI scanner. Measurements were done by two independent raters, blinded to patients and controls, using a custom method for computer assisted manual segmentation. The volumes were normalized for intracranial volume which was also measured manually. The paired t test and Wilcoxon’s signed rank test were used for the main statistical analysis.ResultsThere was no significant difference with respect to left, right or total hippocampal volume between patients and controls. All mean differences were close to zero, and the two-tailed 95% confidence interval for the difference in total, normalized volume does not include a larger than 8% deficit in the patients.ConclusionThe study gives solid evidence against the hypothesis that the patients’ lowered quality of life was due to a major reduction of hippocampal volume.

Compromised quality of life in adult patients who have received a radiation dose towards the basal part of the brain. A case-control study in long-term survivors from cancer in the head and neck region

BackgroundAdult patients with hypothalamic-pituitary disorders have compromised quality of life (QoL). Whether this is due to their endocrine consequences (hypopituitarism), their underlying hypothalamic-pituitary disorder or both is still under debate. The aim of this trial was to measure quality of life (QoL) in long-term cancer survivors who have received a radiation dose to the basal part of the brain and the pituitary.MethodsConsecutive patients (n=101) treated for oropharyngeal or epipharyngeal cancer with radiotherapy followed free of cancer for a period of 4 to10 years were identified. Fifteen patients (median age 56 years) with no concomitant illness and no hypopituitarism after careful endocrine evaluation were included in a case-control study with matched healthy controls. Doses to the hypothalamic-pituitary region were calculated. QoL was assessed using the Symptom check list (SCL)-90, Nottingham Health Profile (NHP), and Psychological Well Being (PGWB) questionnaires. Level of physical activity was assessed using the Baecke questionnaire.ResultsThe median accumulated dose was 1.9 Gy (1.5–2.2 Gy) to the hypothalamus and 2.4 Gy (1.8–3.3 Gy) to the pituitary gland in patients with oropharyngeal cancer and 6.0–9.3 Gy and 33.5–46.1 Gy, respectively in patients with epipharyngeal cancer (n=2). The patients showed significantly more anxiety and depressiveness, and lower vitality, than their matched controls.ConclusionIn a group of long time survivors of head and neck cancer who hade received a low radiation dose to the hypothalamic-pituitary region and who had no endocrine consequences of disease or its treatment QoL was compromised as compared with well matched healthy controls.

Thyroid hormone receptor-β gene expression in the brain of the frog Pelophylax esculentus: Seasonal, hormonal and temperature regulation

Thyroid hormone receptor-β (trβ) cDNA was identified in the adult of Pelophylax esculentus (previously: Rana esculenta), a seasonally breeding species, in order to detect spatial brain trβ expression, its levels through the seasons and in response to 6-n-propyl-2-thiouracil, T4 and T3 administrations as well as to thermal manipulations. The deduced amino acid sequence of P. esculentus trβ showed a high similarity to the homologous of other vertebrates. By in situ hybridization we found trβ mRNA signal in the anterior preoptic nucleus, the habenulae, the hypothalamic-pituitary region and the ependyma. Brain trβ transcript levels varied through the seasons, and they were well correlated with brain T4 levels but only partially with T3 levels. Experimentally-induced hypothyroidism decreased brain trβ expression. The administration of exogenous thyroid hormones increased brain trβ expression, with T4 appearing more potent than T3. The experiments of thermal manipulations further strengthen the hypothesis that T4 is more effective than T3 in brain trβ regulation. This study also shows that, as in other vertebrates, deiodinase enzymes could modulate trβ expression via thyroid hormone regulation.

Approach to the Patient with Persistent Hyperprolactinemia and Negative Sellar Imaging

Hyperprolactinemia is a common cause of menstrual disturbances affecting young women. There is a diversity of causes, from physiological, such as pregnancy, to pharmacological and pathological, such as hypothyroidism. Renal and hepatic failure, intercostal nerve stimulation by trauma or surgery, prolactinomas, other tumors in the hypothalamus-pituitary region, as well as macroprolactinemia can also be considered. Identifying the correct cause is important to establish the correct treatment. Should all these causes be ruled out and pituitary imaging revealed as negative, idiopathic hyperprolactinemia is therefore diagnosed. In symptomatic patients, treatment with dopaminergic agonists is indicated. As for the asymptomatic hyperprolactinemic individuals, macroprolactinemia should be screened, and once it is detected, there is no need for pituitary imaging study or for dopaminergic agonist use.

Clinical Case Seminar. Peculiar prolactinomas in patients with pituitary developmental gene mutations: from an adult endocrinologist perspective

Congenital hypopituitarism is a syndrome which is associated with single or multiple pituitary hormone deficiencies. Mutations in a number of developmental genes have been linked to combined pituitary hormone deficiencies, the most common being mutation in the pituitary homeobox protein prophet of the Pit 1 gene (PROP1). PROP1 exhibits DNA-binding and transcriptional activities. On magnetic resonance imaging, most patients with PROP1 mutation have a hypoplastic pituitary gland. Occasionally, transient pituitary enlargement before definite involution is reported. Kallmann syndrome (KS) is a human developmental genetic disorder which is a clinically (isolated hypogonadotropic hypogonadism-IHH) and genetically heterogeneous disease. Routine neuroimaging in classical IHH is thought to be of limited clinical value and normal anatomy of the hypothalamic-pituitary region is often reported. For neither disorder are there many reports on imaging during adulthood. Nor are there any guidelines concerning long-term imaging follow-up in patients with developmental pituitary disorders. Our aim was to present unusual endocrine and imaging abnormalities which developed in adulthood in two patients with developmental pituitary disorders. We report a female with combined pituitary hormone deficiencies (GH, TSH, gonadotropin and ACTH), except for prolactin, as a consequence of PROP1 mutation, and a male with KS (anosmia and IHH) due to Kal 2 gene (fibroblast growth factor receptor 1- FGFR1) mutation, both of whom in adulthood presented with prolactinomas. Both patients with developmental gene mutations, after long-term correction of their sex steroid status, developed prolactinomas. Although the exact mechanism of pituitary tumorigenesis is not known, we speculate that sex steroids may have facilitated prolactinoma development from the prolactin cell pool which underwent uncontrolled proliferation in the setting of a developmental disorder.

Treatment of patients with hypothalamic-pituitary lesions as adult-onset Langerhans cell histiocytosis

We report four cases of adult-onset Langerhans cell histiocytosis (LCH) with central nervous system (CNS) lesions in the hypothalamic-pituitary region. The first clinical symptoms were diabetes insipidus (two patients), hypothyroidism (one patient), and decreased libido/erectile dysfunction (one patient). Diagnosis was delayed as the CNS lesion was not initially suspected to be secondary to LCH, with a median time from symptom onset to treatment of 3.0 (range <1-5.3) years. In three patients, the tumor mass was effectively reduced by chemotherapy; however, all patients continue to exhibit hypopituitarism. Early diagnosis and initiation of treatment are required to improve the outcome of CNS-LCH in adult patients.