deamino-arginine-vasopressin and Germinoma

We report the case of a pituitary stalk germinoma initially misdiagnosed and treated as infundibuloneurohypophysitis (INH). A 27-year-old man presented with a 1-year history of polydipsia, polyuria, nycturia consistent with central diabetes insipidus and a hyperintense pituitary stalk lesion on MRI. A possible INH diagnosis was considered, after excluding other pathologies. Lesion biopsy was discarded at that time on the ground of a small target and the high risk of added morbidity. Oral desmopressin led to initial symptoms resolution but, in the following months, an anterior panhypopituitarism developed, in spite of appropriate treatment and, by that time, the brain MRI also revealed lesion growth, which prompted a biopsy recommendation. The pathology analysis revealed a germinoma. After chemotherapy and radiotherapy, there was complete disappearance of the pituitary lesion, but the panhypopituitarism persisted. In conclusion, this case highlights the importance and difficulty of precise diagnosis in the initial assessment of pituitary stalk lesions and the need for close monitoring of treatment response. Diagnostic reassessment and biopsy in atypical cases is the only path to achieve the correct diagnosis and treatment.

Topics: Adult; Autoimmune Hypophysitis; Biopsy; Chemoradiotherapy; Deamino Arginine Vasopressin; Diabetes Insipidus, Neurogenic; Diagnosis, Differential; Drug Monitoring; Germinoma; Hormone Replacement Therapy; Hormones; Humans; Hydrocortisone; Hypopituitarism; Magnetic Resonance Imaging; Male; Pituitary Gland; Pituitary Neoplasms; Thyroxine; Treatment Outcome

The pituitary bright spot is acknowledged to indicate functional integrity of the posterior pituitary gland, whilst its absence supports a diagnosis of central diabetes insipidus (DI). This feature was evaluated, together with the incidence and clinical characteristics of DI in children with suprasellar/neurohypophyseal germinomas. We performed a review of all suprasellar (SS) or bifocal (BF) germinoma pediatric patients treated in Toronto since 2000. Demographics, symptomatology, treatment outcome and imaging were evaluated. Nineteen patients fulfilled inclusion criteria (10 SS, 9 BF; median age 12.5 years (6.2-16.8 years)). All remained alive at 6.4 years median follow-up (1.2-13.7 years) after receiving chemotherapy and radiotherapy (13 focal/ventricular, four whole brain, two neuraxis), with only one progression. All had symptoms of DI at presentation with a symptom interval above one year in eight cases (42 %). Desmopressin was commenced and maintained in 16 patients (84 %). The pituitary bright spot was lost in most diagnostic interpretable cases, but was appreciated in three patients (18 %) who had normal serum sodium values compared to 'absent' cases (p = 0.013). For two such cases, spots remained visible until last follow-up (range 0.4-3.3 years), with one still receiving desmopressin. No case of bright spot recovery was observed following therapy. Protracted symptom intervals for germinoma-induced central DI may reflect poor clinical awareness. Explanations for persistence of the pituitary bright spot in symptomatic patients remain elusive. Desmopressin seldom reverses the clinical features of germinoma-induced DI to allow discontinuation, nor does treatment cause bright spot recovery.

Topics: Adolescent; Central Nervous System Neoplasms; Child; Deamino Arginine Vasopressin; Diabetes Insipidus; Female; Follow-Up Studies; Germinoma; Hormones; Humans; Magnetic Resonance Imaging; Male; Pituitary Gland; Retrospective Studies; Sodium; Treatment Outcome

A 14-year-old girl weighing 32 kg was diagnosed with suprasellar tumor causing hydrocephalus, hypothyroidism, adrenal dysfunction and central diabetes insipidus. She was treated with levothyroxine and hydrocortisone and urged to take fluid to replace urine. She was scheduled to undergo ventricular drainage to relieve hydrocephalus prior to tumor resection. For the first surgery, desmopressin was not started and urine output reached 4,000 to 6,000 ml x day(-1), urine osmolality 64 mOsm x l(-1) and urine specific gravity 1.002. Anesthesia was induced with sevoflurane and maintained with propofol and remifentanil. Maintenance fluid was with acetated Ringer's solution and urine loss was replaced with 5% dextrose. Bradycardia and hypotension occurred after intubation, which was treated with volume load. Infusion volume was 750 ml and urine output was 1100 ml during 133 min of anesthesia. Postoperative day 1 nasal desmopressin was started. Ten days later, partial tumor resection was performed. Anesthesia was induced with propofol and fentanyl and maintained with sevoflurane and remifentanil. Infusion volume was 610 ml, urine output 380 ml, and blood loss 151 ml during 344 min of anesthesia. Hemodynamic parameters were stable throughout the procedure. Pathology of the tumor was revealed to be germinoma. Bradycardia and hypotension experienced during the first surgery was suspected to be caused by preoperative hypovolemia brought by polyuria. Desmopressin was proved to be effective to treat excessive urine output and to maintain good perioperative water balance.

Topics: Adolescent; Anesthesia, General; Antidiuretic Agents; Brain Neoplasms; Cerebrospinal Fluid Shunts; Deamino Arginine Vasopressin; Diabetes Insipidus, Neurogenic; Female; Germinoma; Humans; Perioperative Care

We report the clinical course of 2 patients with central diabetes insipidus and evolving to panyhypopituitarism which prompted the diagnosis of an isolated pituitary stalk thickening (PST). In both patients, all etiological investigations were normal and the first biopsy revealed an isolated lymphocytic infiltrate with no sign of malignancy. Close clinical follow-up accompanied by serial brain MRIs was proposed to determine a precise diagnosis and for early detection and treatment of neoplastic disease. In our first case, the diagnosis of germinoma was made 9 months after the PST diagnosis owing to tumor progression. In the second case, the time course was even longer with the diagnosis of germinoma 6 years following initial presentation. In these cases, it is speculated that the lymphocytic infiltrates represent the first sign of a host reaction to an occult germinoma. To our knowledge, this is the third case reported of lymphocytic infiltrates preceding a germinoma in a prepubertal girl, and the only case reported in a prepubertal boy. These cases underline the difficulties in establishing the diagnosis of germinoma in a patient with isolated PST.

Topics: Child; Child, Preschool; Deamino Arginine Vasopressin; Diabetes Insipidus, Neurogenic; Diagnosis, Differential; Female; Germinoma; Human Growth Hormone; Humans; Hypopituitarism; Lymphocytes; Magnetic Resonance Imaging; Male; Pituitary Gland; Pituitary Gland, Anterior; Thyroxine

Germinoma represents 7.8% of cerebral tumors in pediatric age and 50-65% of germ cell cerebral tumors. Generally it is a definite lesion of the pineal gland or suprasellar region, frequently occurring in the first three decades of life. Clinical presentation depends on tumor localization. Pineal lesions generally determine symptoms due to the compression of cerebral structures, causing Parinaud syndrome, while hypothalamic lesions are often characterized by diabetes insipidus, hypopituitarism and visual defects. In the absence of these classic signs and symptoms, however, the diagnosis of germinoma can be difficult. We presented the case of an 8-year-old boy, referred to our clinic for polyuria and polydipsia. Hormonal evaluations demonstrated central diabetes insipidus (CDI), with normal anterior pituitary function. Magnetic resonance imaging (MRI) showed a lack of posterior pituitary gland and partial pituitary stalk enlargement. The patient started therapy with desmopressin (Minirin) with good hydro-electrolytic balance. During follow-up the pituitary function became insufficient with low growth velocity. A second MRI demonstrated a bifocal lesion with dyshomogeneous and cystic appearance, suggesting the diagnosis of germinoma. On the basis of this case report we would like to point out the importance of an early diagnosis in order to improve the prognosis of the disease and the necessity of a careful follow-up of these patients.

Topics: Antidiuretic Agents; Antineoplastic Combined Chemotherapy Protocols; Child; Deamino Arginine Vasopressin; Diabetes Insipidus; Diagnosis, Differential; Drug Therapy, Combination; Germinoma; Humans; Male; Pituitary Neoplasms; Treatment Outcome

We present here a case of prominent hypercalcemia accompanied by hypothalamic tumor and Graves' disease. A 24-year-old man with hypothalamic tumor showed hypopituitarism, central diabetes inspidus (DI) and hyperthyroidism. Nausea, loss of thirst and appetite, and general fatigue were found with the unveiling of hypercalcemia and hypernatremia. Parathyroid hormone (PTH) and 1alpha-dihydroxyvitamin D levels were suppressed with a normal range of PTH-related protein values. One-desamino-(8-D-arginine)-vasopressin (DDAVP) and half-saline administration normalized hypernatremia, while hypercalcemia was still sustained. Administration of cortisone acetate and thiamazole reduced the elevated serum Ca level. In the present case, concurrent hyperthyroidism was assumed to accelerate skeletal mobilization of calcium into the circulation. Hypocortisolism and central DI was also considered to contribute, to some extent, to the hypercalcemia through renal handling of Ca.

Topics: Adult; Antithyroid Agents; Calcitriol; Calcium; Cortisone; Craniotomy; Deamino Arginine Vasopressin; Diabetes Insipidus; Drug Therapy, Combination; Germinoma; Graves Disease; Humans; Hypercalcemia; Hypernatremia; Hyperthyroidism; Hypopituitarism; Hypothalamic Neoplasms; Magnetic Resonance Imaging; Male; Methimazole; Parathyroid Hormone; Parathyroid Hormone-Related Protein; Peptide Fragments; Proteins; Renal Agents; Sodium; Teratoma

Topics: Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Child; Craniotomy; Deamino Arginine Vasopressin; Diabetes Insipidus, Neurogenic; Etoposide; Female; Germinoma; Humans; Hypopituitarism; Pituitary Gland, Anterior; Pituitary Neoplasms; Renal Agents

A 13-year-old boy's acute onset of diabetes insipidus was the first manifestation of a pineal tumor. One year after the physical symptoms of diabetes insipidus occurred, neurological examinations, tumor markers, and computed tomography brain scan were all normal. Three years later, rapid development of neurological changes was observed with the prevailing symptoms of increased intracranial pressure. The changes were related to a pineal germ cell tumor identified by a high level of beta-human chorionic gonadotropin in plasma and neuroradiological investigations, including computed tomography and magnetic resonance imaging. The clinical course of this case is unusual and we advocate the following: (1) the follow-up of children with diabetes insipidus is important for determining whether or not it is an idiopathic type and (2) elevation of plasma beta-human chorionic gonadotropin and development of neurological signs in patients with so-called idiopathic diabetes insipidus should arouse clinical suspicion of an intracranial germ cell tumor. It should be noted that the brain tumor is significant as the underlying pathology of childhood diabetes insipidus.

Topics: Administration, Intranasal; Adolescent; Biomarkers, Tumor; Brain Neoplasms; Chorionic Gonadotropin; Chorionic Gonadotropin, beta Subunit, Human; Deamino Arginine Vasopressin; Diabetes Insipidus; Germinoma; Humans; Male; Peptide Fragments; Pineal Gland