[Effect of growth hormone supplementation on liver and lung function in patients with hypopituitarism].

To analyze the clinical features of patients with anterior hypopituitarism (HP) complicated with cirrhosis, and to explore the effects of growth hormone supplementation on liver and lung function. A total of 11 patients with HP complicated with cirrhosis admitted to Peking Union Medical College Hospital from January 2016 to December 2022 were included in the study, including 8 males and 3 females, aged [M(Q1, Q3)]31 (20, 37) years. There were 6 patients with pituitary stalk interruption syndrome, 4 patients after craniopharyngioma resection, and 1 patient after germinal cell tumor chemoradiotherapy. Cirrhosis appeared at [M(Q1, Q3)]7 (1, 16) years after the diagnosis of HP. There were 7 cases complicated with hepatopulmonary syndrome (HPS). The liver and lung function of 5 patients were improved significantly after the addition of growth hormone, and the arterial partial pressure of oxygen increased from (47±11) mmHg(1 mmHg=0.133 kPa) to (84±12) mmHg. Timely supplementation of growth hormone can improve the symptoms of fatty liver, cirrhosis and HPS, and postpone or even avoid the transplantation of liver and other organs.

Tocilizumab for the fifth progression of cystic childhood craniopharyngioma-a case report.

We present the case of a 15-year-old girl, with a fifth cystic progression of an adamantinomatous craniopharyngioma after multiple surgeries and previous local radiotherapy. She had severe visual impairment, panhypopituitarism including diabetes insipidus, and several components of hypothalamic damage, including morbid obesity and severe fatigue. To prevent further late effects hampering her quality of survival, she was treated biweekly with intravenous tocilizumab, an anti-interleukin-6 agent, which stabilized the cyst for a prolonged time. Based on the biology of adamantinomatous craniopharyngioma, this immune-modulating treatment seems promising for the treatment of this cystic tumor in order to reduce surgery and delay or omit radiotherapy.

Why do patients with hypopituitarism still present an increased mortality?

Hypopituitarism is defined as a lack or decreased secretion of one or several pituitary hormones. It can result from diseases of the pituitary gland or from pathologies of the superior regulatory center, i.e. the hypothalamus, thereby decreasing hypothalamic releasing hormones and consequently the pituitary hormones. It is still a rare disease with an estimated prevalence of 30-45 patients/100,000 and an incidence of 4-5/100,000/year. This review summarizes the currently available data with a focus on etiologies of hypopituitarism, evidence on mortality rates in patients with hypopituitarism, temporal trends in mortality , and associated diseases, pathophysiological mechanisms and risk factors that affect mortality risk in these patients.

A novel diagnostic tool for the evaluation of hypothalamic-pituitary region and diagnosis of growth hormone deficiency: pons ratio.

Backgrounds Limitations in the evaluation of the pituitary size and changes according to pubertal status make its validity questionable. Recently, in a small-scale study, pons ratio (PR) has been suggested as a more sensitive tool for diagnosis and etiological evaluation of growth hormone deficiency (GHD). The aim of the study is to evaluate the diagnostic value of PR in the diagnosis of GHD. Methods We retrospectively evaluated the pituitary magnetic resonance imaging (MRI) of 133 patients with a diagnosis of GHD. Primary axis (PA) was assigned as a line crossing the mid-sagittal dorsum sella and fourth ventricle. PR was defined as the pons height above the PA divided by total pons height. The PR of patients with GHD was compared to subjects without GHD. Results Study included 133 patients with GHD and 47 controls. In total, 121 (91%) patients had isolated GHD and 12 (9%) patients had multiple pituitary hormone deficiency. The PR of the patient group (mean: 0.32 ± 0.89; range: 0.14-0.63) was significantly higher than controls (mean: 0.26 ± 0.067; range 0.19-0.44) (p: 0.000). The optimal cut-off value of PR for GHD diagnosis was 0.27 (sensitivity 71% specificity 56%). There was a negative correlation between anterior pituitary height (APH)-SDS and PR (p: 0.002; r: -0.27). APH was increased, but PR remained unchanged in pubertal patients (p: 0.089). Conclusions PR measurement is a noninvasive, practical method with a cost-benefit clinical value. As it is not affected by pubertal status, PR is potentially a more sensitive tool for evaluation of pituitary gland in GHD patients compared to APH.

Otx2b mutant zebrafish have pituitary, eye and mandible defects that model mammalian disease.

Combined pituitary hormone deficiency (CPHD) is a genetically heterogeneous disorder caused by mutations in over 30 genes. The loss-of-function mutations in many of these genes, including orthodenticle homeobox 2 (OTX2), can present with a broad range of clinical symptoms, which provides a challenge for predicting phenotype from genotype. Another challenge in human genetics is functional evaluation of rare genetic variants that are predicted to be deleterious. Zebrafish are an excellent vertebrate model for evaluating gene function and disease pathogenesis, especially because large numbers of progeny can be obtained, overcoming the challenge of individual variation. To clarify the utility of zebrafish for the analysis of CPHD-related genes, we analyzed the effect of OTX2 loss of function in zebrafish. The otx2b gene is expressed in the developing hypothalamus, and otx2bhu3625/hu3625 fish exhibit multiple defects in the development of head structures and are not viable past 10 days post fertilization (dpf). Otx2bhu3625/hu3625 fish have a small hypothalamus and low expression of pituitary growth hormone and prolactin (prl). The gills of otx2bhu3625/hu3625 fish have weak sodium influx, consistent with the role of prolactin in osmoregulation. The otx2bhu3625/hu3625 eyes are microphthalmic with colobomas, which may underlie the inability of the mutant fish to find food. The small pituitary and eyes are associated with reduced cell proliferation and increased apoptosis evident at 3 and 5 dpf, respectively. These observations establish the zebrafish as a useful tool for the analysis of CPHD genes with variable and complex phenotypes.

Are hypothalamic- pituitary (HP) axis deficiencies after whole brain radiotherapy (WBRT) of relevance for adult cancer patients? - a systematic review of the literature.

BACKGROUND: Cranial radiotherapy (cRT) can induce hormonal deficiencies as a consequence of significant doses to the hypothalamic-pituitary (HP) axis. In contrast to profound endocrinological follow-up data from survivors of childhood cancer treated with cRT, little knowledge exists for adult cancer patients. METHODS: A systematic search of the literature was conducted using the PubMed database and the Cochrane library offering the basis for our debate of the relevance of HP axis impairment after cRT in adult cancer patients. Against the background of potential relevance for patients receiving whole brain radiotherapy (WBRT), a particular focus was set on the temporal onset of hypopituitarism and the radiation dose to the HP axis. RESULTS: Twenty-eight original papers with a total of 1728 patients met the inclusion criteria. Radiation doses to the HP area ranged from 4 to 97 Gray (Gy). Hypopituitarism incidences ranged from 20 to 93% for adult patients with nasopharyngeal cancer or non-pituitary brain tumors. No study focused particularly on hypopituitarism after WBRT. The onset of hypopituitarism occurred as early as within the first year following cRT (range: 3 months to 25.6 years). However, since most studies started follow-up evaluation only several years after cRT, early onset of hypopituitarism might have gone unnoticed. CONCLUSION: Hypopituitarism occurs frequently after cRT in adult cancer patients. Despite the general conception that it develops only after several years, onset of endocrine sequelae can occur within the first year after cRT without a clear threshold. This finding is worth debating particularly in respect of treatment options for patients with brain metastases and favorable survival prognoses.

Pituitary pathology in traumatic brain injury: a review.

PURPOSE: Traumatic brain injury most commonly affects young adults under the age of 35 and frequently results in reduced quality of life, disability, and death. In long-term survivors, hypopituitarism is a common complication. RESULTS: Pituitary dysfunction occurs in approximately 20-40% of patients diagnosed with moderate and severe traumatic brain injury giving rise to growth hormone deficiency, hypogonadism, hypothyroidism, hypocortisolism, and central diabetes insipidus. Varying degrees of hypopituitarism have been identified in patients during both the acute and chronic phase. Anterior pituitary hormone deficiency has been shown to cause morbidity and increase mortality in TBI patients, already encumbered by other complications. Hypopituitarism after childhood traumatic brain injury may cause treatable morbidity in those survivors. Prospective studies indicate that the incidence rate of hypopituitarism may be ten-fold higher than assumed; factors altering reports include case definition, geographic location, variable hospital coding, and lost notes. While the precise pathophysiology of post traumatic hypopituitarism has not yet been elucidated, it has been hypothesized that, apart from the primary mechanical event, secondary insults such as hypotension, hypoxia, increased intracranial pressure, as well as changes in cerebral flow and metabolism may contribute to hypothalamic-pituitary damage. A number of mechanisms have been proposed to clarify the causes of primary mechanical events giving rise to ischemic adenohypophysial infarction and the ensuing development of hypopituitarism. CONCLUSION: Future research should focus more on experimental and clinical studies to elucidate the exact mechanisms behind post-traumatic pituitary damage. The use of preventive medical measures to limit possible damage in the pituitary gland and hypothalamic pituitary axis in order to maintain or re-establish near normal physiologic functions are crucial to minimize the effects of TBI.

The role of autoimmunity in pituitary dysfunction due to traumatic brain injury.

PURPOSE: Traumatic brain injury (TBI) is one of the most common causes of mortality and long-term disability and it is associated with an increased prevalence of neuroendocrine dysfunctions. Post-traumatic hypopituitarism (PTHP) results in major physical, psychological and social consequences leading to impaired quality of life. PTHP can occur at any time after traumatic event, evolving through various ways and degrees of deficit, requiring appropriate screening for early detection and treatment. Although the PTHP pathophysiology remains to be elucitated, on the basis of proposed hypotheses it seems to be the result of combined pathological processes, with a possible role played by hypothalamic-pituitary autoimmunity (HPA). This review is aimed at focusing on this possible role in the development of PTHP and its potential clinical consequences, on the basis of the data so far appeared in the literature and of some results of personal studies on this issue. METHODS: Scrutinizing the data so far appeared in literature on this topic, we have found only few studies evaluating the autoimmune pattern in affected patients, searching in particular for antipituitary and antihypothalamus autoantibodies (APA and AHA, respectively) by simple indirect immunofluorescence. RESULTS: The presence of APA and/or AHA at high titers was associated with an increased risk of onset/persistence of PTHP. CONCLUSIONS: HPA seems to contribute to TBI-induced pituitary damage and related PTHP. However, further prospective studies in a larger cohort of patients are needed to define etiopathogenic and diagnostic role of APA/AHA in development of post-traumatic hypothalamic/pituitary dysfunctions after a TBI.

Major Issues of Care in Thalassemia Major Children Refugees.

Beta thalassemia major (ßTM) is the most common inherited hemoglobinopathy. Management essentially focuses on preventing and treating complications. Conventional treatment is based on a regular blood transfusion program, and chelation therapy. Management essentially focuses on preventing and treating complications. Severe complications of ßTM are very rarely seen in children in Europe. In the context of the migrant crisis, pediatricians will be confronted with the challenge of managing severe complicated ßTM. We report the case of 2 Syrian 10-year-old twin girls who arrived to France with numerous and severe complications of ßTM: hemochromatosis, alloimmunization, hypopituitarism, osteopenia… Their clinical management, which led to successful vital and functional improvement, is reported in this article.

Hypothalamic hypopituitarism secondary to suprasellar metastases from small cell lung cancer: a case report and review of the literature.

BACKGROUND: Metastasis to the pituitary gland is an infrequent clinical problem, and the symptoms caused by metastases have been reported in only 2.5-18.2% of the cases. However, metastasis to the suprasellar lesion has rarely been reported in the literature. To the best of our knowledge, only nine cases of hypothalamic hypopituitarism due to metastases of solid tumors have been reported in English-language journals. CASE PRESENTATION: A 67-year-old Japanese man presented to our hospital with generalized weakness, lethargy, and weight loss. Laboratory data showed hypoglycemia together with low thyroid-stimulating hormone and free thyroxine. We suspected hypopituitarism and performed imaging of the head, which revealed multiple tumors, one of which was in the suprasellar region. Computed tomography of the chest showed a tumor shadow, and a bronchoscopic biopsy pathologically showed small cell lung cancer. Hormone profiling demonstrated hypothalamic pan-hypopituitarism. We diagnosed hypothalamic hypopituitarism secondary to metastases from the primary lung cancer and initiated radiation, chemotherapy, and hormone replacement, but the patient died 10 months later. CONCLUSIONS: We report a case of a 67-year-old man with hypothalamic hypopituitarism secondary to a suprasellar metastasis from a primary small cell lung cancer, and we review ten cases of hypothalamic hypopituitarism due to metastases, including our patient. Recognizing hypopituitarism can be challenging, especially in the elderly, whose symptoms such as lethargy and visual decline may be mistaken for the natural aging process. In patients with established metastatic conditions, the symptoms may be wrongly attributed to malignancy or to the side effects of therapy. When a patient is suspected of having hypopituitarism, a hormone load test can help to diagnose the type of hypopituitarism. It is important to evaluate the brain and the whole body to confirm whether metastasis and primary cancer exist. Because the mortality rate is very high, aggressive intervention for both diagnosis and therapy is required in cases of hypothalamic hypopituitarism secondary to tumor metastasis.

The Hypothalamic-Pituitary Axis and Autoantibody Related Disorders.

This review summarized different studies reporting the presence of autoantibodies reacting against cells of the pituitary (APAs) and/or hypothalamus (AHAs). Both APAs and AHAs have been revealed through immunofluorescence using different kinds of substrates. Autoantibodies against gonadotropic cells were mainly found in patients affected by cryptorchidism and hypogonadotropic hypogonadism while those against prolactin cells were found in different kinds of patients, the majority without pituitary abnormalities. APAs to growth hormone (GH) cells have been associated with GH deficiency while those against the adrenocorticotropic cells have distinguished central Cushing's disease patients at risk of incomplete cure after surgical adenoma removal. AHAs to vasopressin cells have identified patients at risk of developing diabetes insipidus. APAs have been also found together with AHAs in patients affected by idiopathic hypopituitarism, but both were also present in different kinds of patients without abnormalities of the hypothalamic-pituitary axis. Despite some data being promising, the clinical use of pituitary and hypothalamus autoantibodies is still limited by the low diagnostic sensitivity, irreproducibility of the results, and the absence of autoantigen/s able to discriminate the autoimmune reaction involving the pituitary or the hypothalamus from the other autoimmune states.

Hypopituitarism in the elderly: a narrative review on clinical management of hypothalamic-pituitary-gonadal, hypothalamic-pituitary-thyroid and hypothalamic-pituitary-adrenal axes dysfunction.

Hypopituitarism is an uncommon and under-investigated endocrine disorder in old age since signs and symptoms are unspecific and, at least in part, can be attributed to the physiological effects of aging and related co-morbidities. Clinical presentation is often insidious being characterized by non-specific manifestations, such as weight gain, fatigue, low muscle strength, bradipsychism, hypotension or intolerance to cold. In these circumstances, hypopituitarism is a rarely life-threatening condition, but evolution may be more dramatic as a result of pituitary apoplexy, or when a serious condition of adrenal insufficiency suddenly occurs. Clinical presentation depends on the effects that each pituitary deficit can cause, and on their mutual relationship, but also, inevitably, it depends on the severity and duration of the deficit itself, as well as on the general condition of the patient. Indeed, indications and methods of hormone replacement therapy must include the need to normalize the endocrine profile without contributing to the worsening of intercurrent diseases, such as those of glucose and bone metabolism, and the cardiovascular system, or to the increasing cancer risk. Hormonal requirements of elderly patients are reduced compared to young adults, but a prompt diagnosis and appropriate treatment of pituitary deficiencies are strongly recommended, also in this age range.

Frequent development of combined pituitary hormone deficiency in patients initially diagnosed as isolated growth hormone deficiency: a long term follow-up of patients from a single center.

BACKGROUND: Children initially diagnosed with isolated GH deficiency (IGHD) have a variable rate to progress to combined pituitary hormone deficiency (CPHD) during follow-up. OBJECTIVE: To evaluate the development of CPHD in a group of childhood-onset IGHD followed at a single tertiary center over a long period of time. PATIENTS AND METHODS: We retrospectively analyzed data from 83 patients initially diagnosed as IGHD with a mean follow-up of 15.2 years. The Kaplan-Meier method and Cox regression analysis was used to estimate the temporal progression and to identify risk factors to development of CPHD over time. RESULTS: From 83 patients initially with IGHD, 37 (45%) developed CPHD after a median time of follow up of 5.4 years (range from 1.2 to 21 years). LH and FSH deficiencies were the most common pituitary hormone (38%) deficiencies developed followed by TSH (31%), ACTH (12%) and ADH deficiency (5%). ADH deficiency (3.1 ± 1 years from GHD diagnosis) presented earlier and ACTH deficiency (9.3 ± 3.5 years) presented later during follow up compared to LH/FSH (8.3 ± 4 years) and TSH (7.5 ± 5.6 years) deficiencies. In a Cox regression model, pituitary stalk abnormalities was the strongest risk factor for the development of CPHD (hazard ratio of 3.28; p = 0.002). CONCLUSION: Our study indicated a high frequency of development of CPHD in patients initially diagnosed as IGHD at childhood. Half of our patients with IGHD developed the second hormone deficiency after 5 years of diagnosis, reinforcing the need for lifelong monitoring of pituitary function in these patients.

Sustained alterations of hypothalamic tanycytes during posttraumatic hypopituitarism in male mice.

Traumatic brain injury is a leading cause of hypopituitarism, which compromises patients' recovery, quality of life, and life span. To date, there are no means other than standardized animal studies to provide insights into the mechanisms of posttraumatic hypopituitarism. We have found that GH levels were impaired after inducing a controlled cortical impact (CCI) in mice. Furthermore, GHRH stimulation enhanced GH to lower level in injured than in control or sham mice. Because many characteristics were unchanged in the pituitary glands of CCI mice, we looked for changes at the hypothalamic level. Hypertrophied astrocytes were seen both within the arcuate nucleus and the median eminence, two pivotal structures of the GH axis, spatially remote to the injury site. In the arcuate nucleus, GHRH neurons were unaltered. In the median eminence, injured mice exhibited unexpected alterations. First, the distributions of claudin-1 and zonula occludens-1 between tanycytes were disorganized, suggesting tight junction disruptions. Second, endogenous IgG was increased in the vicinity of the third ventricle, suggesting abnormal barrier properties after CCI. Third, intracerebroventricular injection of a fluorescent-dextran derivative highly stained the hypothalamic parenchyma only after CCI, demonstrating an increased permeability of the third ventricle edges. This alteration of the third ventricle might jeopardize the communication between the hypothalamus and the pituitary gland. In conclusion, the phenotype of CCI mice had similarities to the posttraumatic hypopituitarism seen in humans with intact pituitary gland and pituitary stalk. It is the first report of a pathological status in which tanycyte dysfunctions appear as a major acquired syndrome.

Pituitary stalk interruption syndrome in 53 postpubertal patients: factors influencing the heterogeneity of its presentation.

BACKGROUND: Pituitary stalk interruption syndrome (PSIS) may induce an isolated growth hormone (GH) deficiency or multiple hypothalamic-pituitary (HP) deficiencies. Patients with multiple HP deficiencies, primarily those with adrenocorticotropin (ACTH) deficiency, are at increased risk of morbidity and mortality. Our objective was to identify the factors influencing each symptom and the MRI features of the syndrome to enhance its diagnosis and genetic analysis. METHODS: This study was a retrospective, single-center, case-cohort study of 53 patients with PSIS who had reached pubertal age. RESULTS: Patients were classified as having an isolated GH deficiency (n = 24, Group 1) or HP deficiencies (n = 29, Group 2); of these, 19 had complete HP deficiency, and 10 had GH deficiency associated with TSH (n = 4), TSH and ACTH (n = 3), TSH and gonadotropin (n = 1) deficiencies or amenorrhea (n = 2). The following features were less frequent in Group 1 than in Group 2: breech presentation (4% vs 35%, P = 0.008), hypoglycemia (0% vs 59%, P<0.00001), micropenis (13% vs 69%, P<0.003), hypothalamic origin (0% vs 52%, P<0.000001), ophthalmic malformation (8% vs 38%, P<0.02) and psychomotor delay (0% vs 31%, P<0.004). The frequencies of all other malformations were similar in both groups (37% vs 59%). A visible pituitary stalk was characteristic of patients belonging to Group 1 (P<0.0002). The GH peak was greater in Group 1 than in Group 2 (P<0.0003), as was the anterior pituitary height (P = 0.01). CONCLUSION: The factors that best discriminate patients with multiple HP deficiencies from those with an isolated GH deficiency are breech presentation, hypoglycemia, and micropenis. No patient with an isolated GH deficiency had psychomotor delay, but associated malformations and/or syndromes, with the exception of ophthalmic disorders, occurred with similar frequencies in both groups. We have also shown that each of the above characteristics is associated with a given HP deficiency and/or malformation/syndrome in the majority of cases.

Rapidly progressing fatal adult multi-organ Langerhans cell histiocytosis complicated with fatty liver disease.

Langerhans cell histiocytosis (LCH) is a clonal neoplasm that shows diverse clinical manifestations and courses of disease progression. The etiology and pathophysiology of LCH remain uncertain. We describe the clinical course of a 23-year-old Japanese woman with multi-system LCH, who showed rapid progression after steroid reduction and developed multi-organ failure. Liver biopsy showed LCH infiltration with fatty degeneration. She was treated with cytarabine, vincristine, and prednisolone according to the Japan LCH study group 02 protocol, without any clinical improvement. Low expression of Ki67 and bcl-2 failed to explain the rapid clinical course. Panhypopituitarism and hypothalamic dysfunction may have caused nonalcoholic fatty liver disease and liver failure. This case indicates that some multi-system LCH patients with hypopituitarism and hypothalamic dysfunction show very rapid progression and are difficult to treat.

Self-formation of functional adenohypophysis in three-dimensional culture.

The adenohypophysis (anterior pituitary) is a major centre for systemic hormones. At present, no efficient stem-cell culture for its generation is available, partly because of insufficient knowledge about how the pituitary primordium (Rathke's pouch) is induced in the embryonic head ectoderm. Here we report efficient self-formation of three-dimensional adenohypophysis tissues in an aggregate culture of mouse embryonic stem (ES) cells. ES cells were stimulated to differentiate into non-neural head ectoderm and hypothalamic neuroectoderm in adjacent layers within the aggregate, and treated with hedgehog signalling. Self-organization of Rathke's-pouch-like three-dimensional structures occurred at the interface of these two epithelia, as seen in vivo, and various endocrine cells including corticotrophs and somatotrophs were subsequently produced. The corticotrophs efficiently secreted adrenocorticotropic hormone in response to corticotrophin releasing hormone and, when grafted in vivo, these cells rescued the systemic glucocorticoid level in hypopituitary mice. Thus, functional anterior pituitary tissue self-forms in ES cell culture, recapitulating local tissue interactions.

Anti-hypothalamus and anti-pituitary antibodies may contribute to perpetuate the hypopituitarism in patients with Sheehan's syndrome.

OBJECTIVE: While anti-pituitary antibodies (APAs) were detected in some patients with Sheehan's syndrome (SS) suggesting an autoimmune pituitary involvement in the development of their hypopituitarism, hypothalamic cell anti-hypothalamus antibodies (AHAs) have not been investigated so far. DESIGN: The aim of this study was to evaluate the presence of AHA and APA in SS patients to verify whether an autoimmune hypothalamic-pituitary process can contribute to their late hypopituitarism. METHODS: Twenty women with SS with a duration of disease ranging from 3 to 40 years (median 25.5 years) were enrolled into the study. Out of 20 patients, 12 (60%) had panhypopituitarism and the others had partial hypopituitarism well corrected with appropriate replacement therapy. None of them had clinical central diabetes insipidus. AHA and APA were investigated by immunofluorescence method in all patients. In addition, a four-layer immunofluorescence method was used to verify whether AHA immunostained vasopressin-secreting cells (AVP-c) or not. RESULTS: AHAs were found in 8 out of 20 (40%) and APAs in 7 out of 20 (35%) patients with titers ranging from 1:32 to 1:128 and 1:16 to 1:32 respectively; however, in none of these positive patients AHA immunostained vasopressin cells. None of controls resulted positive for both antibodies. CONCLUSIONS: Patients with SS, even many years after the onset of SS, can show antibodies to pituitary and/or hypothalamic but not AVP-secreting cells. Antibodies to unknown hypothalamic cells (releasing factor-secreting cells) other than APAs suggest that an autoimmune process involving both the hypothalamus and pituitary gland may contribute to late pituitary dysfunction in SS patients.

Primary hypothalamic lymphoma with panhypopituitarism presenting as stiff-man syndrome.

We report an unusual case of primary hypothalamic lymphoma with hypopituitarism presenting as Stiff-man syndrome (SMS). A 64-year-old man was hospitalized due to a 3-week history of general weakness, anorexia, vomiting, weight loss, and muscle pain and spasms precipitated by motion and tactile stimuli resulting in muscle stiffness and difficulty in mobility. Physical examination revealed normal sensorimotor function and reflexes, except for bitemporal visual field defect. Routine laboratory and gastrointestinal examinations provided no remarkable clues. Endocrine assessment revealed low levels of morning cortisol, thyroxine, and anterior pituitary hormones but an increase in prolactin level. The patient's muscle pain and stiffness improved dramatically within 2 days after hydrocortisone therapy and thyroxine replacement. Magnetic resonance imaging (MRI) of the brain confirmed an 18-mm enhancing hypothalamic tumor with optic chiasm involvement, which proved to be a B-cell lymphoma. The results of the extensive studies for systemic lymphoma were negative, suggesting a primary hypothalamic lymphoma. The tumor regressed completely and was invisible on MRI scan after adjuvant radiotherapy. The patient's condition was satisfactory and there was no recurrence of SMS during the 2-year follow-up period. This case demonstrated that primary hypothalamic lymphoma complicated with adrenal insufficiency may manifest as SMS. Early diagnosis and prompt intervention can lead to a favorable outcome and reduce morbidity.