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Hypothalamic hamartomata are benign malformations of the brain consisting of heterotopic nervous tissue, and are often associated with precocious puberty and gelastic seizures in early childhood. We report for the first time the melatonin plasma values of a girl with central precocious puberty and gelastic seizures due to a hypothalamic hamartoma. The melatonin plasma levels were low for the chronological age but appropriate for the pubertal status, making a causal relationship between lowered melatonin plasma levels and precocious puberty possible.

The authors report gigantism in a 16-month-old boy with an extensive optic pathway glioma infiltrating into somatostatinergic pathways, as revealed by magnetic resonance imaging and immunocytochemical studies. Stereotactic biopsies of areas showing hyperintense signal abnormalities on T2-weighted images in and adjacent to the involved visual pathways provided rarely obtained histological correlation of such areas. The patient received chemotherapy, which resulted in reduction of size and signal intensity of the tumor and stabilization of vision and growth velocity.

A 6.5-year-old boy developed seizures at age 2.8 years consisting of episodes of unconsciousness and laughing attacks. By age 6 years, multiple seizure types, including generalized tonic-clonic (GTC), complex partial (CPS) and akinetic seizures, and drop attacks were occurring several times daily. EEG showed multifocal epileptic discharges. Antiepileptic drugs (AEDs) did not control the seizures. With progression of the epilepsy, cognitive deterioration developed. There were no manifestations of precocious puberty. Neuroimaging disclosed a suprasellar mass in continuity with the hypothalamus, and a diagnosis of hypothalamic hamartoma was made. After surgical resection of the hamartoma, the seizures were completely alleviated, and the epileptic EEG discharges disappeared. Improvement of mental function was also noted.

We describe a 21-year-old man presenting with proximal muscle weakness associated with hypernatremia. His manifestations other than muscle weakness included dry skin, loss of axillary and pubic hair, decreased libido and loss of thirst sensation. His serum sodium level was elevated to 169-171 mEq./l but all other electrolytes were normal. In addition, serum CK was elevated and an EMG study showed myogenic changes. Endocrinological studies revealed hypothalamic hypopituitarism, while MRI revealed a suprasellar mass. A partial correction of hypernatremia led to an immediate recovery of the muscle weakness as well as a normalization of both the serum CK level and EMG findings, suggesting a direct association between the muscle weakness and hypernatremia. The phosphocreatine/inorganic phosphorus (PCr/Pi) ratios in the resting calf muscle, obtained using 31P magnetic resonance spectroscopy (MRS), were very low during the state of muscle weakness, while they returned to nearly normal values after clinical improvement, suggesting that the muscle weakness in hypernatremic state was caused by a depletion of the intramuscular energy stores, probably due to an overworking Na-K pump to correct the intracellular electrolyte imbalance.

The case of a 39-year-old man with von Recklinghausen's disease, presenting with emaciation and a marked increase in serum growth hormone concentration, is presented. Neuroradiological and histological examination confirmed anaplastic astrocytoma in the optic chiasm-hypothalamic region. This is a rare case of diencephalic syndrome and von Recklinghausen's occurring together in an adult.

A child is described who has skeletal malformations, gelastic epilepsy, precocious puberty and a hypothalamic hamartoma. The skeletal abnormalities were detected at birth, she developed gelastic epilepsy at the age of 3 years 5 months and precocious puberty at 3 years 8 months. A hypothalamic hamartoma was found on MRI. The precocious puberty has been successfully medically managed, though her seizures are difficult to control. The combination of all four features has not been described previously.

We present the cases of two children with presumed idiopathic central diabetes insipidus whose follow-up MR studies eventually revealed hypothalamic tumors. Thin-section sagittal T1-weighted MR with gadolinium administration is important in the evaluation of these children, and serial examinations are probably necessary.

Nine patients suffering from severe amenorrhoea following neurosurgical or radiotherapy for pituitary tumour or craniopharyngeoma were treated with pulsatile gonadotrophin releasing hormone (GnRH) administration. Seven patients did exhibit ovulatory cycles when GnRH was administered i.v. at a dose of 20 micrograms/pulse, but not at lower doses or when GnRH was administered s.c. Pulsatile GnRH administration may be used to assess the functional integrity of pituitary gonadotrophs and to distinguish pituitary from hypothalamic site of lesion resulting in hypogonadotrophic hypogonadism. It may also be used successfully for treatment of infertility in such patients.

Little is known about what pathways subserve mirth and its expression laughter. We present three patients with gelastic seizures and laughter elicited by electrical stimulation of the cortex who provide some insight into the mechanisms of laughter and its emotional concomitants. The first patient had seizures manifested by laughter without a subjective feeling of mirth. Magnetic resonance imaging showed a cavernous haemangioma in the left superior mesial frontal region. Ictal subdural electrode recording showed the seizure onset to be in the left anterior cingulate gyrus. Removal of the lesion and of the seizure focus rendered the patient virtually seizure free over 16 months of follow-up. The other two patients had complex partial seizures of temporal lobe origin. Electrical stimulation of the fusiform gyrus and parahippocampal gyrus produced bursts of laughter accompanied by a feeling of mirth. These cases reveal a high likelihood of cingulate and basal temporal cortex contribution to laughter and mirth in humans, and suggest the possibility that the anterior cingulate region is involved in the motor act of laughter, while the basal temporal cortex is involved in processing of laughter's emotional content in man.

The LHRH-secreting hypothalamic hamartoma (HH), a congenital malformation consisting of a heterotopic mass of nervous tissue that contains LHRH neurosecretory neurons attached to the tuber cinereum or the floor of the third ventricle, can cause true or central precocious puberty (TPP). We have suggested that it functions as an ectopic LHRH pulse generator independent of the central nervous system inhibitory mechanism that normally restrains the hypothalamic LHRH pulse generator. TPP associated with a hamartoma has all of the hormonal hallmarks of puberty, including a pubertal pattern of pulsatile LH and a pubertal plasma LH response to LHRH administration. Little is known about the natural history of HH. We present long term data on 10 children (5 females and 5 males) with TPP due to HH. Physical signs of puberty were observed at a mean age of 2.2 +/- 1.6 yr (range, 0.5-5.1). Two of 10 had a pedunculated mass, and 8 of 10 had a sessile mass. The hamartoma varied in diameter from 4-25 mm and did not change with time (3.5-8.7 yr). Four patients have a seizure disorder, 3 with gelastic seizures (1 with mental retardation) and 1 with tonic-clonic seizures. The shape of the hamartoma, sessile or pedunculated, did not correlate with the occurrence of seizures. At presentation with sexual precocity, the mean height SD for chronological age was +3.5 +/- 0.4, the mean height SD for bone age was -1.9 +/- 0.4, and the mean bone age SD for chronological age was +6.8 +/- 0.7. Baseline data were comparable to those of 10 females with idiopathic TPP. Nine of 10 HH patients and all idiopathic TPP patients were treated with a LHRH agonist. The response to therapy was excellent in both groups and indistinguishable. Nine of 10 HH children attend school regularly and, aside from those with seizures, have no neurological handicap. While surgical resection of the hamartoma has been recommended, it carries an increased risk of morbidity and mortality and, if removal is incomplete, does not arrest the sexual precocity. In our experience, LHRH agonist therapy for TPP due to HH is the preferable approach.

We reported a 6-month-old boy, patient of hypothalamic hamartoma with a rare association of poly- and syndactyly, which developed gelastic seizures and precocious puberty. His birth was complicated by poly- and syndactyly in both hands and polydactyly in both feet, but other physical signs were normal. At 5 month of age, he visited our hospital because of a suspected seizure. On admission, physical and neurological examinations revealed increased size in penis and testes, and delayed psychomotor development. Gelastic seizures occurred up to 100 times a day, and were resistant to many anticonvulsants. Ictal EEG showed bursts of generalized high voltage slow waves. His serum LH and testosterone levels were elevated for his age. Brain CT and MRI demonstrated a hypothalamic mass lesion, which proved to be hamartoma by biopsy.

We report the case of a 10-year-old girl with a mature teratoma in the hypothalamic region. The patient presented a 2-month history of anorexia, psychic disturbances and a 37% loss of body weight. These symptoms had led initially to a diagnosis of major depression and atypical anorexia nervosa. She also presented some signs and symptoms of diencephalic syndrome. This case illustrates the importance of considering a slow-growing mass as a rare but real possibility in the differential diagnosis of anorexia nervosa, mainly in atypical cases.

Objective: To determine if improved delineation of hypothalamic-pituitary neuroanatomy by magnetic resonance imaging, especially the posterior pituitary hyperintense T1 signal, can be correlated with anterior and posterior pituitary endocrine function., Design: Children with ectopic posterior pituitary tissue were identified at the Endocrine Clinic of the Children's Hospital of Pittsburgh (Pa) and their records were reviewed., Participants: Ten children with ectopic posterior pituitary tissue., Measurements: Anterior pituitary hormone status, determined by standard testing, was correlated with the morphologic anomalies of the hypothalamic-pituitary region on magnetic resonance imaging., Results: Patients were categorized by the appearance of the pituitary stalk based on the magnetic resonance image: attenuation of the stalk (group 1) or nonvisualization of the stalk (group 2). Patients in group 1 retained partial anterior pituitary function. Patients in group 2 had panhypopituitarism., Conclusion: Prospective evaluation of affected individuals may provide insight into the pathophysiologic mechanisms of idiopathic hypopituitarism.

Ten children, five boys and five girls with true precocious puberty at an early age were found to have hypothalamic hamartomas on brain imaging. Very early onset of puberty, varying from a few weeks to three years of age, and rapid progression were characteristic. Accelerated growth velocity and markedly advanced bone age were evident in all. Gonadotropin and gonadal hormone levels were elevated above the prepubertal range. Six children had associated developmental delay or hyperactivity.

A case is reported of intractable epilepsy associated with a hypothalamic hamartoma in an 18 year old man. The patient underwent a two-third anterior callsotomy and, subsequently, removal of the hamartoma. Callosotomy did not affect the generalized seizure pattern. The authors believe this to be the first documented case of hypothalamic hamartoma in which callosotomy for seizure control was attempted. The poor response to callosotomy suggests the extracallosal diffusion of the generalized seizures from hypothalamic hamartomas.

We retrospectively studied 12 consecutive patients with gelastic seizures and hypothalamic hamartomas who, because of intractable epilepsy, underwent chronic intracranial EEG monitoring or epilepsy surgery. All patients had medically refractory seizures that included laughter as an ictal behavior (gelastic seizures). The hypothalamic hamartomas were identified with neuroimaging studies (12 of 12) and by pathologic verification (four of 12). Associated clinical features included behavioral disorders (n = 5), developmental delay (n = 4), and precocious puberty (n = 2). Interictal extracranial EEG predominantly showed bi-hemispheric epileptiform changes suggesting a secondary generalized epileptic disorder. Intracranial EEG recordings, performed in eight patients, indicated the apparent focal onset of seizure activity (anterior temporal lobe [n = 7] and frontal lobe [n = 1]). None of the seven patients who underwent a focal cortical resection, however, experienced a significant reduction in seizure tendency. An anterior corpus callosotomy, performed in two patients with symptomatic generalized epilepsy, resulted in a worthwhile reduction in drop attacks. Results of this study may modify the surgical strategies in patients with gelastic seizures and hypothalamic hamartomas.

A 62-year-old male with small cell lung cancer (SCLC) associated with Cushing's syndrome and diabetes insipidus (DI) is reported. The patient was referred to our hospital for treatment of SCLC. A diagnosis of paraneoplastic Cushing's syndrome was made on the basis of an elevated serum ACTH (623.5 pg/ml) level, elevated excretion of urinary 17-OHCS (18.01 mg/day), obesity, hypertension, hyperglycemia, persistent hypokalemia, alkalosis, and no history of diabetes mellitus. He was also diagnosed as having DI based on polyuria and polydipsia, low specific gravity of the urine (1.007-1.010), low serum ADH (1.4 pg/ml) level, normal plasma osmolarity (29 mOsm/kg H2O), and the results of water deprivation test. DI and a left visual field defect was suggestive of metastasis to the pituitary region, but no lesion was detected by either CT scan or MRI scan. The patient failed to show a good response to intensive chemotherapy, and died of the tumor five months after commencing chemotherapy. Post-mortem examination revealed metastases to the hypothalamic-neurohypophyseal region, lungs, liver, adrenal glands, bone, bone marrow, and hilar and mediastinal lymph nodes.

A 61 year old man presented with chronic bronchitis, which he had been suffering from for many years, and reported the recent onset of polyuria with polydipsia. A chest X-ray showed a peripheral pulmonary nodule in the right lower lobe, that was diagnosed as small cell lung cancer following histological examination of the pulmonary tissue specimen, obtained with transbronchial biopsy. After establishing the central origin of the diabetes insipidus, its cause was revealed by magnetic resonance imaging of the brain, that demonstrated metastasis to the hypothalamic-neurohypophyseal area.

A hypothalamic hamartoma associated with true precocious puberty in a 7-month-old girl is hereby reported. Hormonal studies disclosed elevated serum levels of luteinizing hormone (LH) and follicle stimulating hormone, both of which responded well to LH-releasing hormone stimulation. Following a subtotal removal of the tumor, the clinical manifestations of precocious puberty as well as associated endocrinological abnormalities returned to normal. The role of surgery for this lesion, which appears to be safe when a planned microsurgical course is employed, is discussed.

Five children, three girls and two boys, were treated for precocious puberty secondary to hypothalamic hamartoma by resection of the hamartoma. The patients' ages at onset of pubertal development ranged from 6 to 19 months. The hamartomas ranged in size from 6 to 10 mm; four were pedunculated, one was sessile, and all were located below the tuber cinereum. The hamartomas were excised via a right subtemporal approach, with transection at the inferior surface of the hypothalamus; two were adherent posteriorly to the basilar artery and brain stem, and the adhesions were divided. Postoperatively, three children exhibited a transient oculomotor paresis and one other child required eye-muscle surgery. The symptoms and signs of precocious puberty completely regressed postoperatively in all patients. Preoperative hormone assays of testosterone, luteinizing hormone, and follicle-stimulating hormone were within the pubertal range in all five children; postoperative assays fell to prepubertal levels. The children have been followed for 0.5 to 10.5 years (mean 5.0 years) postoperatively, without evidence of recurrence of precocious puberty. One child has begun spontaneous puberty at a normal age. It is concluded that complete resection of hypothalamic hamartomas causing precocious puberty is curative.

Hypothalamic hamartoma is reported to be associated with precocious puberty. Here, the authors present a seven-year-old girl whose onset of puberty occurred at the age of two. Under the impression of idiopathic precocious puberty, cyproterone acetate was initially tried. Since the effect of her medication was not satisfactory, it was discontinued at the age of five years and 11 months. However, rapid advance of bone age and vaginal spotting recurred after the withdrawal of treatment. She was re-evaluated at the age of six, and a magnetic resonance image (MRI) study of the head revealed a hypothalamic hamartoma. At that time, a long-acting analog of luteinizing hormone-releasing hormone (LHRHa), leuprolide acetate, was prescribed. Her secondary sex characteristics regressed and her hypothalamic-pituitary-gonad axis was suppressed after treatment. The clinical presentation, mechanism and treatment of precocious puberty caused by hypothalamic hamartomas are fully discussed in this report.

Gelastic (laughing) epilepsy, relatively uncommon, is usually associated with hypothalamic hamartomas, pituitary tumors, astrocytomas of the mammillary bodies, and dysraphic conditions. Cases of unknown etiology are rare. In three of the four cases reported here, the diagnoses were hamartoma of the tuber cinereum; lobar holoprosencephaly; and lissencephaly type I, grade 2. In the fourth, radiographic investigation gave a normal result; a genetic etiology was suggested because of bilateral familial idiopathic epilepsy. In all patients, EEGs showed both focal spikes and generalized spike-and-wave discharges. The primary underlying neurophysiologic disorder may be provoked by the diffuse hyperexcitability of the cortex and subsequent firing of the thalamocortical networks with which the cortical brain is reciprocally interlinked.

We report on a case of neonatal hypothalamic hamartoblastoma with holoprosencephaly, Hirschsprung disease, and tetramelic postaxial polydactyly. Twenty-seven previous cases of congenital hypothalamic embryonic tumours with associated congenital defects are reviewed. A classification in isolated, associated, and syndromal forms is proposed. The difficulties encountered in differential diagnosis between the syndromal form (mainly represented by the Pallister-Hall syndrome) and related diseases as Smith-Lemli-Opitz type II, holoprosencephaly-polydactyly, orofaciodigital type VI and hydrolethalus syndromes are outlined. Two pathogenic mechanisms are discussed: a classical pleiotropic model and single sequence model. The latter is sufficient to delineate syndromal hypothalamic hamartoblastoma. With the former, syndromal hypothalamic hamartoblastoma cannot be clearly recognized in the absence of a CNS tumour, a child with syndromal hypothalamic hamartoblastoma cannot be reliably diagnosed as Pallister-Hall rather than another MCA syndrome, and, ultimately, the existence of Pallister-Hall syndrome could be questioned, as it could only be the extreme expression of one or several other syndromes. As this hypothesis cannot be proven or disproven at this point, the authors suggest creating the concept of multiplex phenotype. "Cerebro-Acro-Visceral Early lethality multiplex syndrome" is suggested to encompass all the ambiguous cases. Within this complex, an operative classification key is proposed.

A case of hypothalamic astrocytoma with precocious puberty is presented. In July 1989, a 2-year-old girl was admitted to our hospital because of vaginal bleeding and enlargement of breasts. Breast development was Tanner's stage 3 and no pubic hair was present. Endocrinological evaluation revealed a slightly high level of LH, but the responses of LH and FSH to LH-RH test resulted in exceedingly high values similar to those in adults. Plain CT scan showed an isodense mass in the suprasellar cistern which was not enhanced following administration of contrast medium. MR imaging revealed the precise location of the mass attached to the posterior hypothalamus between the pituitary stalk and the mamillary bodies in sagittal view. The signal intensity of the mass was homogenous and isointense relative to the gray matter on T1 weighted image. But on T2 weighted image, it showed high signal intensity compared with the normal brain parenchyma. A right fronto-temporal craniotomy was performed and the tumor was partially removed. Histological examination disclosed moderate hypercellularity of glial cells but no neurons were visible. This appeared to be astrocytoma grade II. In the literature, CT and MRI behaviour of hypothalamic hamartomas are almost similar to our case. Therefore we think it is not possible at the present time to differentiate a low grade astrocytoma from hamartoma when using CT and MRI alone. In this case, the mechanism of development of precocious puberty seemed to be due to hypothalamic compression by the tumor.

Cranial magnetic resonance imaging was performed in 17 children with central precocious puberty (CPP) and 19 aged-matched controls to compare the appearance of the pituitary gland. Gland size was measured on T1-weighted sagittal and coronal images. The gland was graded according to the concavity or convexity of the upper surface, and the signal intensity of the gland was assessed visually. The mean pituitary volume in 13 CPP children without hypothalamic tumor (292.6 mm3) was significantly greater than that in normal controls (181.35 mm3). The mean volume for the four CPP children with hypothalamic tumor was smaller (145.0 mm3). Compared to controls, the upper pituitary surface in CPP patients appeared convex in a higher proportion. The anterior pituitary was isointense to pons in all patients and controls. Although the posterior pituitary bright spot was present in 14 controls and 11 CPP patients, none with hypothalamic tumor showed it.

The authors report the case of a young woman with advanced breast cancer who developed diabetes insipidus due to pituitary involvement and also gastric metastases. This patient had a normal brain CT scan. Gastric metastases were diagnosed when she was operated for a perforated gastric ulcer. Although very rare, and even if the brain CT scan is normal, pituitary metastases should be diagnosed in the presence of suggestive clinical symptoms. Abdominal pain also warrants investigation in these patients in an early attempt to document any possible gastric metastases.

Four cases of hypothalamic hamartoma leading to gelastic epilepsy, precocious puberty and behavioural disorders are reported. Cerebral neuroradiologic examinations revealed a tumor-like mass attached to the hypothalamus in the region of the mamillary bodies in all cases. Precocious puberty developed in the two girls at 4 and 13 months but in neither of the two boys, who both suffered behaviour disturbances in the form of aggressive outbursts. A total resection of the tumors of both boys led to histologic confirmation of hamartoma. One boy was free of seizures upon follow-up, whereas seizure frequency in the other boy was reduced, while his aggressivity increased. The cases are discussed in context of current therapeutic conceptions of gelastic epilepsy and central precocious puberty.

Hypothalamic hamartomas may cause a peculiar epileptic syndrome characterized by seizures of laughter and precocious puberty. Four mentally handicapped patients suffering from gelastic epilepsy were referred to our institution for investigation; three of them also presented with precocious puberty. In all four cases magnetic resonance imaging (MRI) revealed a space-occupying lesion of the hypothalamus that was considered to be a hamartoma. Biopsies were not performed. Hamartomas appear isodense in plain computed tomography scans, and they do not enhance. Such lesions display an isointense signal in T1-weighted magnetic resonance images and a hyperintense signal in proton density and T2-weighted images. MRI is the procedure of choice for detecting such lesions at the base of the brain.

A 7 year old girl presented with precocious puberty and ictal laughter. Brief, repetitive, stereotyped attacks of laughter were the first manifestation of the epileptic syndrome. Stages of puberty were noted as B III-IV and PH II according to Tanner. X-rays showed a bone age of 11 years and the weight increased from the 50th beyond 97th percentile. Plasma concentrations of LH, FSH, testosterone and Ostradiol were elevated. The CT scan was normal and a magnetic resonance imaging showed an hypothalamic hamartoma. The control of the seizures control and social adjustment were poor. MR scanning 3 years later showed no change in the size of the lesion.

Infants and young children with the diencephalic syndrome exhibit a normal activity level despite profound marasmus. Investigation reveals an intracranial tumour and evidence of endocrine dysfunction. The condition is easily missed in Third World countries with a high prevalence of nutritional marasmus. The advent of computer tomography and magnetic resonance imaging has simplified diagnosis. The syndrome was diagnosed in 1981 in a boy of 20 months who had a large hypothalamic tumour. Initial endocrine studies revealed very high growth hormone levels. After radiotherapy, these levels reverted to normal for a time but have subsequently declined in keeping with a state of hypopituitarism. The boy's long-term survival has afforded an opportunity for study over eight years. During this time, growth has been slow but sustained. There has been some fall off in intellectual capacity. Characteristic features of the diencephalic syndrome are normal activity and a state of euphoria in a profoundly marasmic child. Investigation reveals the presence of an intracranial tumour and evidence of endocrine dysfunction. Though there are earlier references, the condition first came to medical attention at the annual meeting of the British Paediatric Association in 1951 when Russell described the typical features. In Third World countries where childhood marasmus is common, the syndrome is easily overlooked. The present report concerns a boy who has been closely followed for more than eight years.

Between March, 1983, and February, 1989, 19 infants or children with chiasmal/hypothalamic gliomas were treated with chemotherapy after either surgical or radiological diagnosis. The patients ranged in age from 15 weeks to 15.6 years (median 3.2 years) at the start of therapy. Twelve patients were treated immediately after diagnosis because of progressive symptoms, and seven received chemotherapy after either radiographic progression or clinical deterioration, including progressive visual loss or intracranial hypertension. Based on biopsy results, seven of these tumors were classified as juvenile pilocytic astrocytomas, two as astrocytomas, two as highly anaplastic astrocytomas, and one as a subependymal giant-cell astrocytoma. There was associated neurofibromatosis in four patients. The two initial patients were treated with either actinomycin D and vincristine or 5-fluorouracil, hydroxyurea, and 6-thioguanine. The remaining patients received nitrosourea-based therapy; 15 evaluable patients were treated with a five-drug regimen that included 6-thioguanine, procarbazine, dibromodulcitol, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), and vincristine and one received 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and 5-fluorouracil. Fifteen of the 18 evaluable patients initially managed with chemotherapy either responded to therapy or their condition stabilized. Median time to tumor progression has not been reached at a median follow-up period of 79 weeks (range 6.6 to 303 weeks), and no tumor-related death has occurred with a median follow-up period of 79 weeks (range 18 to 322 weeks) from the initiation of therapy. The four patients who failed therapy or whose disease progressed after chemotherapy were treated satisfactorily with radiation therapy. Initial improvement or stabilization of visual function was obtained in 16 patients. Endocrine function remained stable in all patients during treatment, although three patients required pharmacological treatment for endocrinopathy that was present at diagnosis. These preliminary results suggest that nitrosourea-based cytotoxic regimens are useful for the initial treatment of children with chiasmal/hypothalamic gliomas, and allow potentially harmful radiation therapy to be deferred until progression of disease.

A 20-year-old woman was diagnosed as hypodipsic hypernatremia syndrome in association with a variety of hypothalamic syndromes. Computed brain tomography disclosed a space occupying lesion over the region of the hypothalamus, lateral ventricle and paraventricles. Evaluation revealed defective osmoregulation of thirst and AVP release and hypothalamic syndrome. She showed no desire to drink at a plasma osmolality of above 320 mOsm/kg. Dissociation in the plasma vasopressin response to osmotic change and hemodynamic change was demonstrated in this patient. Treatment with a vasopressin analogue, desamino-D-arginine vasopressin and forced intake of water restored plasma osmolality and serum sodium levels to normal. In this case, selective osmoregulating dysfunction was presumably associated with pathologic conditions in or around the hypothalamus.

The neuroimaging studies, clinical evaluations, and surgical and pathologic findings in five children with biopsy-proved hamartomas of the tuber cinereum were reviewed. Surgical and/or MR findings showed that patients with precocious puberty had pedunculated lesions while those with seizures had tumors that were sessile with respect to the hypothalamus. The radiologic studies included six MR examinations in four patients and CT studies in all five patients. Three children presented with precocious puberty and two with seizures, one of which was a gelastic (spasmodic or hysteric laughter) type of epilepsy. MR studies were obtained both before and after surgery in two patients, only preoperatively in a third patient, and only postoperatively in the fourth child. MR was superior to CT in displaying the exact size and anatomic location of the hamartomas in all cases. The mass was isointense with gray matter on sagittal and coronal T1-weighted images, which best displayed the relationship of the hamartoma to the third ventricle, infundibulum, and mammillary bodies. Intermediate- or T2-weighted images showed signal characteristics of the hamartoma to be isointense (one case) or hyperintense (two cases) relative to gray matter. The difference in T2 signal intensity did not correlate with any obvious differences in histopathology. CT showed attenuation isodense with gray matter, and no calcium. There was no enhancement on CT. There was no enhancement on MR in the one case in which contrast medium was administered. Preservation of the posterior pituitary bright spot was noted on all pre- and postoperative T1-weighted MR scans.(ABSTRACT TRUNCATED AT 250 WORDS)

The purpose of this study was to determine whether the MR findings of idiopathic pituitary dwarfism correlated with a clinical history of perinatal abnormalities and abnormal levels of pituitary hormones. MR examinations of 18 patients with pituitary dwarfism were performed; these patients were divided into two groups: those with ectopic posterior lobes (group 1) and those with normal posterior lobes (group 2). Among the seven patients in group 1, MR showed hyperintense signal at the median eminence of the hypothalamus, which was regarded as the ectopic posterior lobe of the pituitary gland. The mean anteroposterior length and height of the pituitary gland in group 1 patients were significantly smaller than those dimensions in the normal control group; the pituitary stalk was not detected in three of seven patients. Six of seven patients were products of breech presentation with perinatal asphyxia. The peak serum growth hormone level was less than 5 ng/ml when assessed by insulin-induced hypoglycemia or the clonidine test. MR findings in the 11 patients with pituitary dwarfism and normal posterior lobes were normal except that the mean size of the pituitary gland was slightly smaller than that of normal controls. The clinical history of these patients was normal except for perinatal asphyxia in one case. Our findings in patients with pituitary dwarfism, with or without an ectopic posterior pituitary lobe suggest that the ectopic lobe, visualized as a bright spot at the median eminence of the hypothalamus, may be common when pituitary dwarfism follows perinatal anoxic/ischemic episodes.

Sellar or parasellar lesions can cause anterior pituitary dysfunction either by direct damage to the anterior pituitary gland or by compression of the pituitary stalk and mediobasal hypothalamus which contain the hypophysiotropic hormones. Without treatment, the pituitary deficits in such cases are not likely to improve. We describe a case in which deficits in anterior pituitary hormones spontaneously remitted in a woman who had a persistent hypothalamic lesion that was not amenable to surgery or radiotherapy. The factors that may predict spontaneous recovery of anterior pituitary function in such cases are discussed.

At age 3 1/2 years a child developed what appeared to be classic spasmus nutans. Thorough discussions as to the propriety of neuroimaging studies in such patients are presented. With this late age of onset, the presence of a compressive lesion was suspected and neuroimaging demonstrated a sellar-suprasellar mass lesion.

To study whether patients with idiopathic GH deficiency (IGHD) show a delayed GH response pattern to GHRH, 42 patients with IGHD, 14 patients with hypothalamic tumor (2ry GHD), and 23 normal short children (NSC) were examined as to their GH response patterns to GHRH together with their TSH and PRL response patterns to TRH. After TRH injection, the mean time of the TSH peak in IGHD (67.5 +/- 6.5 min, n = 36) and 2ry GHD patients (81.7 +/- 14.8 min, n = 9) was clearly delayed comparing to that of NSC (29.1 +/- 2.9 min, n = 16; both p less than 0.01). Similarly, the mean time of the PRL peak in IGHD (38.3 +/- 3.6 min, n = 36) and 2ry GHD patients (39.5 +/- 5.8, n = 11) was significantly delayed comparing to NSC (22.0 +/- 3.5 min, both p less than 0.01). In IGHD patients, the delayed response pattern of TSH and PRL was more remarkable in patients who had breech delivery than in those with normal delivery. In contrast, the mean time of the GH peak was similar in IGHD (62.1 +/- 4.0 min, n = 41), 2ry GHD (64.1 +/- 8.1 min, n = 11) and NSC (58.0 +/- 6.1 min, n = 23). However, the decline from peak GH (120 min GH/peak GH) was significantly smaller in IGHD (54.3 +/- 4.2%) and 2ry GHD (60.7 +/- 7.3%) than in NSC (39.0 +/- 8.1%) (both p less than 0.05). Further, in IGHD patients plasma GH response was greater in patients with normal delivery than in those with breech and asphyxia delivery. These results seem to indicate: 1) the stimulus-secretion mechanism is different between somatotrophs and thyrotrophs or lactotrophs in man, 2) IGHD patients have hypothalamic lesions as well as pituitary lesions, 3) such hypothalamo-pituitary lesions in IGHD patients are greater in patients with abnormal delivery than in those with normal delivery.

This report describes some effects of premature production of sex hormones observed in a boy with precocious puberty. The data presented are compared with corresponding skeletal and oral factors in an unaffected monozygous twin brother.

We describe four male patients with hypothalamic hamartomas associated with sexual precocity. Our assessment of their management suggests that resection using current microsurgical techniques is a valid treatment option if the patient has a normal pubertal endocrine makeup, if the hamartoma is pedunculated, and if the patient is young enough to require years of parenteral medical treatment. Such surgical treatment can be curative, and subsequent growth and development can be normal (patients 1 and 2). However, if the patient is near to pubertal age (patient 3) or if neurosurgical or gonadotropin releasing hormone analogue treatment is not available, the natural history (patient 4) suggests that the only undesirable effects are accelerated growth, tall stature for age, and premature sexual development during childhood, as well as the psychosocial problems that may accompany them. Adult height may be compromised, although the two patients who did not undergo a surgical procedure and did not receive gonadotropin releasing hormone analogue therapy are above the lower limits of the normal range of adult male height. Therefore, if the hamartoma is pedunculated and cessation of pubertal development is desired, resection of the hamartoma is a reasonable therapeutic option.

An elderly case of secondary hypothermia associated with brain tumor was reported. An 84-year old woman developed hypothermia. Although her rectal temperature remained below 37 degrees C, the circadian rhythm of rectal temperature was preserved. Brain computerized tomography (CT) and brain magnetic resonance imaging (MRI) revealed a solitary brain tumor involving the hypothalamus. It appears that her hypothermia may not be due to inability to thermoregulate but to stem from her abnormal target temperatures. Body temperature is normally controlled at around 37 degrees C, but in this patient thermoregulation might have been reset at a lower temperature.

The height and age at presentation of 458 children beginning treatment with growth hormone between January 1980 and June 1984 were retrospectively analysed. Three hundred and nine children with isolated growth hormone deficiency had a mean (SD) age of 10 (4.1) years on beginning treatment and a mean (SD) height standard deviation score (SDS) of -3.73 (0.93). One hundred and nine patients with hypothalamopituitary tumours began treatment with growth hormone on average 3.3 years after diagnosis of the tumour and at a mean (SD) height SDS of -2.42 (1.49). In both of these categories the height SDS showed a considerable improvement compared with previous reports. Forty two patients with growth hormone deficiency secondary to cranial irradiation started treatment with growth hormone on average 6.1 years after treatment for their tumours and had a height SDS of -2.45 (1.02) compared with that of -2.45 (0.98) seen in nine similar patients from the United Kingdom starting treatment with growth hormone between 1975 and 1978. Although closer surveillance of short children in the community is leading to earlier diagnosis of growth hormone deficiency, this could possibly be diagnosed earlier if routine screening of height was to be carried out at school entry. In addition, patients who have received cranial irradiation should be regularly measured and investigated when their height velocity becomes subnormal.

This case report describes a hypothalamic hamartoma with multiple congenital abnormalities in a male infant, with a post-mortem examination and histology of the lesion.

Three children with diencephalic tumours are described. In these cases, the main clinical features are extreme emaciation and nystagmus. Ultrasonography and computed tomography demonstrated the tumour. In one case, high levels of growth hormone were observed. In the three cases, the tumour was a glioma.