Fanconi syndrome, diabetes insipidus, and acute kidney injury due to tenofovir disoproxil fumarate: A case report.

BACKGROUND: Tenofovir disoproxil fumarate is widely used in Botswana as part of the first-line antiretroviral regimen in the 'Treat All' strategy implemented in 2016 by the Ministry of Health. Its use has been associated with several uncommon adverse renal effects, though rarely all in conjunction or without the combined use of protease inhibitors. CASE PRESENTATION: A 49-year-old woman living with HIV whose viral load is suppressed on tenofovir disoproxil fumarate, lamivudine, and dolutegravir presented with 1 day of generalized weakness and myalgia causing an inability to ambulate. This was associated with nausea and vomiting and profound fatigue. She was found to have an acute kidney injury, non-anion-gap metabolic acidosis, hypernatremia, hypokalemia, and hypophosphatemia. Urinalysis revealed pyuria with white blood cell casts, glucosuria, and proteinuria. The diagnosis was made of tenofovir-induced nephrotoxicity. The tenofovir was discontinued, and the patient was initiated on intravenous fluids and electrolyte and bicarbonate supplementation with improvement in her symptoms and laboratory values. CONCLUSIONS: This report suggests the possibility of severe tenofovir-induced nephrotoxicity with combined acute kidney injury, Fanconi syndrome, and nephrogenic diabetes insipidus in the absence of other provoking factors such as use with protease inhibitors or advanced HIV disease, chronic kidney disease, and age. With its wide use in Botswana and other countries, health-care providers should have a high index of suspicion for tenofovir-induced nephrotoxicity for HIV patients on tenofovir with deranged renal function tests and electrolytes.

Outcome of Radical Surgical Resection for Craniopharyngioma with Hypothalamic Preservation: A Single-Center Retrospective Study of 1054 Patients.

OBJECTIVE: A retrospective review of the surgical outcome for patients with craniopharyngioma (CP) treated in a single neurosurgical center with surgical resection using visualization to ensure hypothalamic preservation. METHODS: The study included 1054 patients. Before 2003, a pterional cranial approach was preferred for 78% of patients; after 2004, the unifrontal basal interhemispheric approach was performed in 79.1% of patients. RESULTS: Complete tumor resection was achieved in 89.6% of patients; vision improved in 47.1% of patients who had preoperative vision impairment. However, diabetes insipidus worsened in 70.4% of patients and new-onset diabetes insipidus occurred in 29.7% of the remaining patients. Pituitary stalk preservation occurred in 48.9% of cases. There were 89.6% of patients with total tumor removal; 13.3% of patients showed tumor recurrence within an average of 2.8 years. Of 69 follow-up patients with a subtotal or partial resection, 94.2% showed tumor recurrence within an average of 4.3 months. Of the total patients, 82.3% fully recovered. CONCLUSIONS: This study has shown that radical surgical resection of CP using microsurgical excision can be effective with a good patient outcome without more limitations on each individual tumor of distinct features despite the impact of recent endoscopic techniques on CP surgery. The surgical approach depends on a direct and wider visualization of CP located in the midline with preserving hypothalamic structures by identifying some hypothalamic landmark structures. After surgery, most patients can resume their normal activities even after aggressive tumor removal, although patients require postoperative hormonal replacement.

The confounding effect of the development of idiopathic orthostatic edema and thyrotoxcosis on weight fluctuation related to effects on free water clearance in a woman with long-standing surgically induced panhypopituitarism and diabetes insipidus.

PURPOSE: To evaluate the effect of idiopathic orthostatic edema and the effect of thyrotoxicosis on weight fluctuation and fluid retention in the presence of surgically induced panhypopituitarism and diabetes insipidus controlled with hormone replacement. MATERIALS AND METHODS: Dextroamphetamine sulfate was used for weight gain when no other etiologic factor was found. Methimazole was used when weight loss occurred when serum T4 and free T4 indicated thyrotoxicosis. RESULTS: Sympathomimetic amine therapy very effectively controlled the weight gain and methimazole controlled the weight loss. CONCLUSIONS: Hypopituitarism and diabetes insipidus controlled with hormone replacement do not protect against fluid retention from idiopathic edema.

Diabetes insipidus as a rare cause of acute cognitive impairment in multiple sclerosis.

Multiple sclerosis (MS) is a complex neurodegenerative disease presenting with a diversity of clinical symptoms including palsy and cognitive impairment. We present a 59-year-old woman with a history of secondary progressive MS since 1987, who was referred to our department because of recent onset of confusion and polydipsia. Initial lab tests showed mildly elevated serum sodium levels and low urine osmolality. Under water deprivation, diuresis and low urine osmolality persisted and serum sodium levels rose above 150 mmol/l. Oral desmopressin resulted in normalisation of serum sodium as well as urine osmolarity, confirming a diagnosis of central diabetes insipidus. As drug-induced diabetes could be excluded, pituitary magnetic resonance imaging (MRI) was performed. A demyelinating lesion was detected in the hypothalamus. The patient was started on oral desmopressin treatment (0.2 mg/day). Fluid intake and serum sodium levels have since remained normal. In summary, we report the rare case of a patient presenting with diabetes insipidus due to progressive MS. Diabetes insipidus should be considered in MS patients who develop new onset of polydipsia.

Pituitary stalk Langerhans cell histiocytosis treated with CyberKnife radiosurgery.

OBJECTIVE: Langerhans cell histiocytosis (LCH) is a rare idiopathic disease that is characterized by clonal proliferation of Langerhans histiocytes in various parts of the body. These atypical cells have been found to infiltrate single or multiple organs, including bone, lungs, liver, spleen, lymph nodes, and skin. Central nervous system invasion in LCH patients has rarely been reported, especially in the adult population. METHODS AND RESULTS: We describe three histopathologically confirmed cases of adult LCH that involves both the pituitary stalk and hypothalamus, and report our limited experience of such cases in this location that has been treated with CyberKnife radio surgery. CONCLUSION: The treatment goal of controlling lesion growth is achieved by CyberKnife radiosurgery in this case series. All patients tolerated the treatment well without obvious complications.

Chronic hypernatremia derived from hypothalamic dysfunction: impaired secretion of arginine vasopressin and enhanced renal water handling.

We analyzed the disorder of water metabolism in a 32 year-old female with chronic hypernatremia. She had meningitis at 4 years, and ventriculo-peritoneal shunt operation at 13 years because of normal pressure hydrocephalus. At 14 years hypernatremia of 166 mmol/l was initially found and thereafter hypernatremia ranging from 150 to 166 mmol/l has been persisted for the last 18 years. Physical and laboratory findings did not show dehydration. Urine volume was 750-1700 ml per day and urinary osmolality (Uosm) 446-984 mmol/kg, suggesting no urinary concentrating defect. Plasma arginine vasopressin (AVP) levels ranged from 0.4 to 1.2 pmol/l despite hyperosmolality of 298 through 343 mmol/kg under ad libitum water drinking. There was no correlation between plasma osmolality (Posm) and plasma AVP levels, but Uosm had a positive correlation with Posm (r=0.545, P < 0.05). Hypertonic saline (500 NaCl) infusion after a water load increased Uosm from 377 to 679 mmol/kg, and plasma AVP from 0.2 to 1.3 pmol/l. There was a positive correlation between Posm and plasma AVP levels in the hypertonic saline test (r=0.612, P<0.05). In contrast, an acute water load (20 ml/kg BW) verified the presence of impaired water excretion, as the percent excretion of the water load was only 8.5% and the minimal Uosm was as high as 710 mmol/kg. Urinary excretion of aquaporin-2 remained low in concert with plasma AVP levels. No abnormality in pituitary-adrenocortical function was found. These results indicate that marked hypernatremia is derived from partial central diabetes insipidus and elevated threshold of thirst, and that enhanced renal water handling may contribute to maintenance of body water in the present subject.

Ovulation induction with pulsatile gonadotropin-releasing hormone (GnRH) or gonadotropins in a case of hypothalamic amenorrhea and diabetes insipidus.

Hypothalamic amenorrhea is a treatable cause of infertility. Our patient was presented with secondary amenorrhea and diabetes insipidus. Cortisol and prolactin responded normally to a combined insulin tolerance test (ITT) and thyrotropin-releasing hormone (TRH) challenge, while thyroid-stimulating hormone (TSH) response to TRH was diminished, and no response of growth hormone to ITT was detected. Both luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels increased following gonadotropin-releasing hormone (GnRH) challenge. No response of LH to clomiphene citrate challenge was detected. Magnetic resonance imaging findings demonstrated a midline mass occupying the inferior hypothalamus, with posterior lobe not visible and thickened pituitary stalk. Ovulation induction was carried out first with combined human menopausal gonadotropins (hMG/LH/FSH) (150 IU/day) and afterwards with pulsatile GnRH (150 ng/kg/pulse). Ovulation was achieved with both pulsatile GnRH and combine gonadotropin therapy. Slightly better results were achieved with the pulsatile GnRH treatment.

Satisfactory remission achieved by PUVA therapy in Langerhans cell hisiocytosis in an elderly patient.

Langerhans cell histiocytosis is currently regarded as a reactive proliferative process of Langerhans cells rather than a malignancy. The disease is characterized by Langerhans cell infiltration of skin, lung, bone and other organs. We report a 74-year-old man with Langerhans cell histiocytosis who had generalized hemorrhagic and crusted papules. He also had diabetes insipidus. Because he did not have any severe constitutional symptoms or failure of vital organs, we applied topical PUVA treatment to his skin lesions, which responded well to the therapy. Diabetes insipidus, however, remained, in spite of X ray radiotherapy for the pituitary lesion.

Histiocytosis X and pregnancy.

BACKGROUND: Histiocytosis X, a clinically heterogeneous infiltrating disorder, is rarely associated with pregnancy. Diabetes insipidus is a common manifestation of histiocytosis X. CASE: A 27-year-old pregnant woman was diagnosed with histiocytosis X by biopsy. At 31 weeks' gestation, she developed diabetes insipidus and required treatment with intranasal 8-D-arginine vasopressin. A hypothalamic mass was noted on magnetic resonance imaging. She delivered a 363-g male at term by cesarean. Two months postpartum, after a motor vehicle accident, she developed a T6 sensory and motor deficit. An intramedullary spinal cord mass was diagnosed and surgically removed. She was treated postoperatively with radiation therapy to the spine and hypothalamus. Despite systemic chemotherapy, the disease progressed, and the patient died 18 months after delivery. CONCLUSION: Pregnancy in patients suffering from histiocytosis X is rare. When pregnancy and histiocytosis X do coincide, diabetes insipidus may appear or worsen. Treatment with intranasal 8-D-arginine vasopressin does not pose risks for the fetus or for premature labor.

Anterior pituitary function and computed tomography/magnetic resonance imaging in patients with Langerhans cell histiocytosis and diabetes insipidus.

In order to document anterior pituitary dysfunction in patients with biopsy-proven Langerhans cell histiocytosis (LCH) and diabetes insipidus and to correlate this with structural changes on imaging, we performed an insulin tolerance test, enhanced computed tomography (CT), and unenhanced magnetic resonance imaging (MRI) in nine patients. Six of the nine patients had growth hormone deficiency, which in two patients was part of panhypopituitarism and in one was associated with poor cortisol response to insulin hypoglycemia. One patient had an exaggerated growth hormone response and one who had had neck irradiation as an infant, had a high resting thyroid stimulating hormone (TSH) suggesting compensated primary hypothyroidism. All enhanced CTs were abnormal, bony defects being the only abnormality in two patients and opaque mastoids in one. The remaining six patients all had structural changes in the hypothalamic/pituitary region. Unenhanced MRI confirmed the CT findings except in one child who had been treated with radiotherapy in the intervening period, but, in addition, confirmed diabetes insipidus by showing absence of the posterior pituitary bright signal and picked up white matter changes in a child with clinical neurological dysfunction. Our findings indicate that the development of diabetes insipidus in LCH is commonly associated with anterior pituitary dysfunction and is usually associated with structural changes in the hypothalamic/pituitary axis.

Anterior and posterior hypopituitarism with pituitary stalk abnormalities.

Hypopituitarism and diabetes insipidus are often idiopathic conditions. A retrospective study of 6 cases of diabetes insipidus and 8 cases of partial or global idiopathic anterior hypopituitarism has shown that MRI is of considerable value to detect abnormalities of the pituitary stalk or hypothalamo-pituitary "relay". On the basis of MRI findings, some cases of idiopathic hypopituitarism can now be grouped together in a new entity which may be called hypopituitarism due to neonatal transection of the pituitary stalk.

Autoimmune cranial diabetes insipidus: its association with other endocrine diseases and with histiocytosis X.

Thirty-nine patients with idiopathic cranial diabetes insipidus (DI) and 81 secondary to hypothalamic lesions were investigated for the presence both of associated autoimmune diseases and autoantibodies. Eleven (28%) of the idiopathic but none of the secondary DI cases had an overt autoimmune disease. A further two patients with idiopathic DI had associated organ-specific autoantibodies. Autoantibodies to vasopressin (AVP)-secreting hypothalamic cells were detected in 12 patients with idiopathic DI (31%). Seven out of 13 cases of DI secondary to histiocytosis X (HX) were also positive (54%), whereas only two (3%) of the other 68 sera from patients with secondary DI reacted with AVP cels. Of the 13 patients with DI associated with frank organ-specific autoimmune diseases or autoantibodies alone, eight (62%) were positive for AVP-cell antibodies. The finding of associated autoimmune diseases in a patient with idiopathic DI is therefore suggestive of an autoimmune origin of DI, and this can be supported by the detection in the serum of AVP cell antibodies. In cases of HX, the new finding of the presence of AVP-cell antibodies reflects hypothalamic infiltration by HX cells, and suggests that DR + 'Langerhans-like' cells play more than a passive role in the hypothalamic lesion.

Thyroid localization in adult histiocytosis X.

Authors report on a rare case of thyroid involvement by histiocytosis X. A 27-yr-old man with diabetes insipidus and lung bullous disease of 2 yr duration was found to have thyroid gland infiltration by differentiated histiocytosis X. This was based on cytological findings consistent with the diagnosis, obtained by fine needle aspiration biopsy. Endocrine studies revealed altered hypothalamic-pituitary function accounted for by a hypothalamic lesion.

[Teratoma of the 4th ventricle and precocious puberty. Case report]. / Teratoma do IV ventrículo e puberdade precoce. Registro de um caso.

A case of precocious puberty and diabetes insipidus in a 7 years old boy due to a malignant teratoma in the IVth ventricle is reported. The tumor had grown into the IIIrd and lateral ventricles as found on the necropsy. The original site of the tumor and the possible physiopathological mechanisms for the precocious puberty are discussed.

The importance of vasopressin in the development and maintenance of DOC-salt hypertension in the rat.

Experiments were performed to determine the role of vasopressin in deoxycorticosterone (DOC)-salt hypertension. In order to determine if vasopressin is necessary for the development of DOC-salt hypertension, rats with hereditary diabetes insipidus (DI) and normal Long-Evans rats (LE) were unilaterally nephrectomized, treated with DOC Pivalate (30 mg/kg . week) and given saline to drink for 8 weeks. A second group of DI rats were unilaterally nephrectomized, but received no treatment. Systolic blood pressure (SBP) increased 40 mm Hg in the LE group (p less than 0.01) but failed to increase significantly in either DI group. Urinary excretion of vasopressin (UADHV) and SBP were measured in unilaterally nephrectomized LE rats treated with DOC and salt (DOC-LE), salt alone (NaCl-LE) and untreated rats (H2O-LE). The UADHV was elevated in DOC-LE (p less than 0.01) and NaCl-LE (p less than 0.05), but only the DOC-LE rats became hypertensive. Finally, the I.V. injection of analogs of vasopressin, which block its pressor but not antidiuretic activity, lowered mean arterial blood pressure 27 +/- 5 mm Hg in 11 conscious DOC-salt hypertensive rats. It is concluded that vasopressin plays a major role as a pressor agent in both the onset and maintenance of DOC-salt hypertension.

Hypothalamic hypothyroidism causing spastic paraplegia: recovery following thyroid medication.

A 63-year-old woman with longstanding spastic paraplegia and neurological evidence of long tract disturbance was found to have hypothyroidism, partial diabetes insipidus, hyperprolactinemia, and gonadotropin deficiency of hypothalamic origin. Replacement therapy with thyroxine and prednisone induced complete remission of the neurological abnormalities. The association of spastic paraplegia with hypothalamic insufficiency has not been reported previously. The possibility of hypothalamic disease should be considered in cases of spastic paraplegia of unknown cause.