Approach To The Pediatric Patient: Central Diabetes Insipidus

Central diabetes insipidus (CDI) is a complex disorder in which large volumes of dilute urine are excreted due to arginine-vasopressin deficiency, and it is caused by a variety of disorders affecting the hypothalamic-posterior pituitary network. The differential diagnosis is challenging and requires a detailed medical history, physical examination, biochemical approach, imaging studies and, in some cases, histological confirmation. Magnetic resonance imaging is the gold standard method for evaluating congenital or acquired cerebral and pituitary stalk lesions. Pituitary stalk size at presentation could be normal, but it may change over time, depending on the underlying condition, while other brain areas or organs may become involved during follow up. Early diagnosis and treatment are crucial in order to avoid central nervous system damage, germ cell tumor dissemination, and to minimize complications of multiple pituitary hormone defects. We provide a practical update on the diagnosis and management of patients with CDI and highlight several pitfalls that may complicate the differential diagnosis of conditions presenting with polyuria and polydipsia. The need for a careful and close follow-up of patients with “apparently” idiopathic CDI is particularly emphasized, because the underlying condition may be recognized over time. The clinical scenario that we outline at the beginning of this article represents the basis for the discussion about how the etiological diagnosis of CDI can be overlooked, and demonstrates how a water intake and urine output improvement can be a sign of progressive damage of both hypothalamus and anterior pituitary gland with associated pituitary hormonal deficiencies.

Outcome of endoscopic transcortical intraventricular biopsy of isolated thickened pituitary stalk lesions in children

OBJECTIVE The purpose of this study was to investigate the efficacy and safety of endoscopic transcortical intraventricular biopsy in pediatric patients with isolated thickened pituitary stalk lesions. METHODS From 1994 to 2018, 16 pediatric patients (8 males and 8 females) underwent endoscopic transcortical intraventricular biopsy at a single institution to establish an accurate pathological diagnosis for appropriate treatment strategies. RESULTS Preoperatively, the median diameter of the pituitary stalks was 5.31 ± 1.67 mm (range 3.86–9.17 mm). Overall, the diagnostic yield at endoscopic intraventricular biopsy was 93.8%. Histopathological diagnosis included germinoma (n = 10, 62.5%), Langerhans cell histiocytosis (n = 4, 25%), pilocytic astrocytoma (n = 1, 6.3%), and pituicytoma (n = 1, 6.3%). Two patients developed new diabetes insipidus after the procedure, and 3 patients had new postoperative hypothyroidism. There were no postoperative neurological deficits in this series. CONCLUSIONS Neuroendoscopic biopsy via the transcortical intraventricular corridor was shown to be safe and to aid in a reliable histopathological diagnosis in the management of isolated pituitary stalk lesions in pediatric patients. It can be considered a minimally invasive alternative to open biopsy via transcranial or endonasal corridors.

Impact of Pituitary Stalk Preservation on Tumor Recurrence/Progression and Surgically Induced Endocrinopathy After Endoscopic Endonasal Resection of Suprasellar Craniopharyngiomas

Objective: To investigate the factors associated with recurrence/progression after endoscopic endonasal resection of suprasellar craniopharyngiomas. Special attention was paid to assess the impact of pituitary stalk preservation on tumor recurrence/progression and endocrinological outcomes.Methods: We retrospectively recruited 73 patients with suprasellar craniopharyngiomas undergone endoscopic endonasal approach (EEA) surgery from September 2014 to May 2019 and assessed their clinical characteristics, surgical outcomes, and recurrence/progression. Stalk preservation or sacrifice was determined by reviewing operative records, videos, and post-operative magnetic resonance imaging.Results: Gross total resection (GTR) was achieved in 51 cases (69.9%). Tumor recurrence was seen in 5 cases (9.8%) and progression was seen in 8 cases (36.4%), respectively. GTR (OR = 0.248 CI 0.081–0.759; p = 0.015) was the only independent factor influencing recurrence/progression. Kaplan-Meier survival analysis showed that the mean recurrence/progression-free survival were 53 (95% CI 48–59) and 39 (95% CI 28–50) months, respectively, in patients with and without GTR (p = 0.011). Pituitary stalk preservation was more common in cases with peripheral type tumors (83% vs. 30%, p < 0.01). Preserving the pituitary stalk does not appear to decrease the percentage of GTR (75.5% vs. 55.0%, p = 0.089), or increase the rate of tumor recurrence (12.5% vs. 0%, p = 0.508) or progression (46.2% vs. 22.2%, p = 0.486). However, surgically induced hypothyroidism (60.5% vs. 100%, p = 0.041) and diabetes insipidus (35.1% vs. 81.8%, p = 0.017) were significantly lower in patients with stalk preservation. For patients who had hypopituitarism before EEA, there was no difference between those with and without stalk preservation regarding post-operative hypopituitarism (p > 0.05).Conclusion: GTR is the only independent predictor of recurrence/progression after EEA surgery for suprasellar craniopharyngiomas. Preserving the pituitary stalk does not appear to increase the risk of non-GTR and tumor recurrence/progression and might help reduce the risk of surgically induced hypothyroidism and diabetes insipidus. We recommend preserving the pituitary stalk in peripheral type suprasellar craniopharyngiomas with normal pituitary function, especially in cases without hypothyroidism or diabetes insipidus. On the other hand, stalk sacrifice could be considered in central type tumors with severe pre-operative endocrinopathy.

Neoplastic Etiology and Natural Course of Pituitary Stalk Thickening: A Systematic Review and Meta-analysis

Context Pituitary stalk thickening (PST) is often identified on magnetic resonance imaging (MRI), either incidentally or during diagnostic work-up of hypopituitarism. However, the neoplastic etiology and natural course of PST are not fully understood, although this knowledge is required to establish diagnostic and surveillance strategies. Objectives To investigate the neoplastic etiology and natural course of PST. Methods MEDLINE/PubMed and EMBASE databases were searched up to February 2021 to identify original research investigating the etiologies of PST. The proportion of neoplastic etiology in patients with PST was meta-analytically pooled. Supplementary analysis exploring factors suggesting neoplasm was also performed. For initially indeterminate cases without confirmed diagnosis, the proportion of patients showing progression of PST during follow-up was evaluated. Results Eighteen studies covering 1368 patients with PST were included. The pooled proportion of neoplasm was 45.2% (95% CI, 33.3–57.8%), with substantial heterogeneity across studies (I 2=93%). The most common neoplasm was germ cell tumor (14.0% of study population), followed by Langerhans cell histiocytosis (10.2%) and metastasis (4.7%). The studies on pediatric populations and those with >50% of patients having at least one pituitary hormone deficiency tended to show a higher proportion of neoplasm. The pituitary stalk was thicker in neoplasms, but the difference was not significant (pooled mean difference, 2.08 mm; P=0.08). In initially indeterminate cases, 18.5% (95% CI, 7.6–38.3%) showed progression of PST during follow-up. Conclusion PST was commonly confirmed to be neoplastic, especially in pediatric populations. As isolated PST frequently progresses, follow-up imaging is essential in initially indeterminate cases.

Dose to neuroanatomical structures surrounding pituitary adenomas and the effect of stereotactic radiosurgery on neuroendocrine function: an international multicenter study

OBJECTIVE Stereotactic radiosurgery (SRS) provides a safe and effective therapeutic modality for patients with pituitary adenomas. The mechanism of delayed endocrine deficits based on targeted radiation to the hypothalamic-pituitary axis remains unclear. Radiation to normal neuroendocrine structures likely plays a role in delayed hypopituitarism after SRS. In this multicenter study by the International Radiosurgery Research Foundation (IRRF), the authors aimed to evaluate radiation tolerance of structures surrounding pituitary adenomas and identify predictors of delayed hypopituitarism after SRS for these tumors. METHODS This is a retrospective review of patients with pituitary adenomas who underwent single-fraction SRS from 1997 to 2019 at 16 institutions within the IRRF. Dosimetric point measurements of 14 predefined neuroanatomical structures along the hypothalamus, pituitary stalk, and normal pituitary gland were made. Statistical analyses were performed to determine the impact of doses to critical structures on clinical, radiographic, and endocrine outcomes. RESULTS The study cohort comprised 521 pituitary adenomas treated with SRS. Tumor control was achieved in 93.9% of patients over a median follow-up period of 60.1 months, and 22.5% of patients developed new loss of pituitary function with a median treatment volume of 3.2 cm3. Median maximal radiosurgical doses to the hypothalamus, pituitary stalk, and normal pituitary gland were 1.4, 7.2, and 11.3 Gy, respectively. Nonfunctioning adenoma status, younger age, higher margin dose, and higher doses to the pituitary stalk and normal pituitary gland were independent predictors of new or worsening hypopituitarism. Neither the dose to the hypothalamus nor the ratio between doses to the pituitary stalk and gland were significant predictors. The threshold of the median dose to the pituitary stalk for new endocrinopathy was 10.7 Gy in a single fraction (OR 1.77, 95% CI 1.17–2.68, p = 0.006). CONCLUSIONS SRS for the treatment of pituitary adenomas affords a high tumor control rate with an acceptable risk of new or worsening endocrinopathy. This evaluation of point dosimetry to adjacent neuroanatomical structures revealed that doses to the pituitary stalk, with a threshold of 10.7 Gy, and doses to the normal gland significantly increased the risk of post-SRS hypopituitarism. In patients with preserved pre-SRS neuroendocrine function, limiting the dose to the pituitary stalk and gland while still delivering an optimal dose to the tumor appears prudent.