High prevalence of anterior pituitary deficiencies after cranial radiation therapy for skull base meningiomas

Background Cranial irradiation represents one of the first line treatment proposed in skull base meningiomas. While cranial irradiation is associated with a high risk of secondary hypopituitarism, few studies focused on the specific location of skull base meningiomas. Methods Fifty-two adults receiving photon-beam therapy for skull base meningiomas between 2003 and 2014 in our Institution were included. Anterior pituitary (ACTH, FSH, GH, LH, TSH and prolactin) as well as corresponding peripheral hormones (8 am-Cortisol, IGF-1, fT3, fT4, 17βestradiol or testosterone) were biologically screened before radiotherapy (baseline), then yearly until March 2019. The pituitary gland (PG) was delineated on CT and the mean dose delivered to it was calculated. Results Mean age at diagnosis was 56 +/− 14 years. Median follow-up was 7 years. Up to 60% of patients developed at least ≥2 pituitary deficiencies, 10 years after radiotherapy. Gonadotroph, thyrotroph, corticotroph and somatotroph deficiencies occurred in 37, 28, 18 and 15% of patients, respectively. Hyperprolactinemia was found in 13% of patients. None patient had only one pituitary deficiency. In the multivariate analysis, a delivered dose to the PG ≥ 50 Gy or a meningioma size ≥40 mm significantly increased the risk of developing hypopituitarism. Conclusions Over a long-term follow-up, cranial radiation therapy used in skull base meningiomas led to a high prevalence of hypopituitarism, further pronounced in case of tumor ≥4 cm. These results advocate for an annual and prolonged follow-up of the pituitary functions in patients with irradiated skull base meningiomas.

LACK OF DELAYED NEUROCOGNITIVE SIDE-EFFECTS OF GAMMA KNIFE RADIOSURGERY IN ACROMEGALY: THE LATER-AC STUDY

Introduction: Persistent growth hormone hypersecretion can be observed in roughly 50% of patients operated for somatotroph adenomas, requiring additional treatments. Despite its proven antisecretory efficacy, the use of Gamma Knife radiosurgery (GK), is limited probably due to the lack of data on long term side effects, including potential cognitive consequences. Methods: The Later-Ac study was a cross sectional exposed/unexposed non randomized study. The primary objective was to determine the long-term neurocognitive effects of GK focusing on memory, executive functions and calculation ability. Exposed patients had been treated by GK for acromegaly at least 5 years before inclusion. Unexposed patients (paired for age) had to be cured or controlled at last follow-up without any radiation technique. Patients of both groups were cured or controlled at last follow-up. Results: 64 patients were evaluated (27 exposed and 37 unexposed). Mean follow-up after GK was 13±6 years (including 24 patients followed for at least 10 years). While up to 23.8% of the patients of the whole cohort presented at least one abnormal cognitive test, we did not observe any significant difference in neurocognitive function between both groups. During the follow-up, 11 patients presented at least one new pituitary deficiency (p=0.009 for TSH deficiency with a higher rate in exposed patients), 2 presented a stroke (1 in each group), and one, a meningioma (12 years after GK). Conclusions: While GK exposes patients to a well-known risk of pituitary deficiency, it does not seem to induce long-term cognitive consequences in patients treated for acromegaly.

Impaired bone microarchitecture in premenopausal women with acromegaly: the possible role of Wnt signaling

Context Acromegaly can impair bone integrity, increasing the risk of vertebral fractures (VF). Objective To evaluate the impact of isolated GH/IGF-I hypersecretion on bone turnover markers,Wnt inhibitors, BMD, microarchitecture, bone strength and vertebral fractures in female patients with acromegaly (Acro), compared to healthy control group (HC). Design, setting, and patients Cross-sectional study including 83 premenopausal women without any pituitary deficiency:18 acromegaly in remission (AcroR), 12 in group with active acromegaly (AcroA) and 53 HC. Serum P1NP, β-CTX, osteocalcin, sclerostin and DKK1 were measured in blood samples. DXA, HR-pQCT and vertebral fractures evaluation were also assessed simultaneously. Main outcome and Results AcroA showed significantly lower sclerostin and higher DKK1 as compared to HC. On HR-pQCT of tibia and radius, Acro showed impairment of trabecular (area and trabecular number), increased cortical porosity and increased cortical area and cortical thickness compared to HC. The only significant correlation found with HR-pQCT parameters was a positive correlation between cortical porosity and serum DKK1 (R=0.45, P=0.044). Mild VF were present in approximately thirty percent of patients. Conclusions Eugonadal women with acromegaly without any pituitary deficiency showed increased cortical BMD, impairment of trabecular bone microstructure and increased VF. Sclerostin was not correlated with any HR-pQCT parameters, however DKK1 was correlated with cortical porosity in tibia (P=0.027). Additional studies are needed to clarify, the role of Wnt inhibitors on bone microarchitecture impairment in acromegaly.

High Prevalence of Anterior Pituitary Deficiencies after Cranial Radiation Therapy for Skull Base Meningiomas.

Background: Cranial irradiation represents the first-line treatment proposed in skull base meningiomas. While cranial irradiation is associated with a high risk of secondary hypopituitarism, few studies focused on the specific location of skull base meningiomas. Methods: 52 adults receiving photon-beam therapy for skull base meningiomas between 1978 and 2014 in our Institution were included. Anterior pituitary (ACTH, FSH, GH, LH, TSH and prolactin) as well as corresponding peripheral hormones (8am-Cortisol, IGF-1, fT3, fT4, 17βestradiol or testosterone) were biologically screened before radiotherapy (baseline), then yearly until March 2019. The pituitary gland (PG) was delineated on CT and the mean dose delivered to it was calculated.Results: Mean age at diagnosis was 56 +/-14 years. Median follow-up was 7 years. Up to 60% of patients developed at least ≥ 2 pituitary deficiencies, 10 years after radiotherapy. Gonadotroph, thyrotroph, corticotroph and somatotroph deficiencies occurred in 37%, 28%, 18% and 15% of patients, respectively. Hyperprolactinemia was found in 13 % of patients. None patient had only one pituitary deficiency. In the multivariate analysis, a delivered dose to the PG ≥ 50 Gy or a meningioma size ≥ 40 mm significantly increased the risk of developing hypopituitarism. Conclusions: Over a long-term follow-up, cranial radiation therapy used in skull base meningiomas led to a high prevalence of hypopituitarism, further pronounced in case of tumor ≥ 4cm. These results advocate for an annual and prolonged follow-up of the pituitary functions in patients with irradiated skull base meningiomas.

Primary empty sella syndrome: Characteristics of the pituitary deficiency. A bicentric case series.

Background and aim Empty sella is the neuroradiological or pathological finding of an apparently empty sella turcica. The aim of the study was to analyze the clinical, hormonal and radiological characteristics of patients with empty sella and to compare anterior pituitary function in total versus partial primary empty sella. Methods The records of 36 patients with primary empty sella were retrospectively analyzed over a 24-years period. The patients were evaluated for pituitary function with basal hormone levels (FT4, TSH, IGF1, FSH, LH, cortisol, ACTH, prolactin) and dynamic testing when necessary. Results Our study included 26 women and 10 men with an average age of 47.64 ±15.47 years. Seventy-six per cent of women were multiparous. Fifteen patients were obese. The revealing symptoms were dominated by endocrine signs (52.7%). More than half of our patients complained of headache. Sixty-one of the patients had partial empty sella and the remaining 39% had total empty sella. Two or more pituitary hormone deficiency were found in 41% of cases. Secondary adrenal insufficiency was the most common pituitary hormone deficiency(41.7%).The percentage of hypopituitarism in complete primary empty sella was significantly higher than that in partial primary empty sella (P<0.05).The management was based on hormone replacement therapy in case of hypopituitarism and on analgesic therapy in case of headache. Conclusion The diagnosis of PES must be evoked in an obese, multiparous, hypertensive woman presenting with a symptomatology suggestive of a pituitary deficiency or chronic headache. The correlation between pituitary gland volume and the degree of hypopituitarism highlights the importance of the early diagnosis and hormones replacement.

A Rare Cause of Pituitary Deficiency: Pituitary Stalk Interruption Syndrome and Magnetic Resonance Imaging Findings

Pituitary stalk interruption syndrome is a rare disease characterized by a deficiency of adenohypophyseal hormones. Clinical presentation usually occurs in childhood or in the second decade of life. The severity of hormonal deficiency is variable. It may be isolated or be accompanied by extra–pituitary anomalies. Magnetic resonance imaging findings are considered as an absent pituitary stalk, absent or smaller adenohypophysis, absent or ectopic neurohypophysis. Contrast-enhanced imaging is essential in evaluating the presence and morphology of the pituitary stalk. In the presence of clinical findings, evaluation of the hypothalamic–pituitary region using magnetic resonance imaging is necessary for diagnosis. Early diagnosed cases can maintain their normal lives with hormone replacement. In this article, we aimed to present pituitary stalk interruption syndrome and its magnetic resonance imaging findings with a case presentation