Significant benefits of AIP testing and clinical screening in familial isolated and young-onset pituitary tumors

Context Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are responsible for a subset of familial isolated pituitary adenoma (FIPA) cases and sporadic pituitary neuroendocrine tumors (PitNETs). Objective To compare prospectively diagnosed AIP mutation-positive (AIPmut) PitNET patients with clinically presenting patients and to compare the clinical characteristics of AIPmut and AIPneg PitNET patients. Design 12-year prospective, observational study. Participants & Setting We studied probands and family members of FIPA kindreds and sporadic patients with disease onset ≤18 years or macroadenomas with onset ≤30 years (n = 1477). This was a collaborative study conducted at referral centers for pituitary diseases. Interventions & Outcome AIP testing and clinical screening for pituitary disease. Comparison of characteristics of prospectively diagnosed (n = 22) vs clinically presenting AIPmut PitNET patients (n = 145), and AIPmut (n = 167) vs AIPneg PitNET patients (n = 1310). Results Prospectively diagnosed AIPmut PitNET patients had smaller lesions with less suprasellar extension or cavernous sinus invasion and required fewer treatments with fewer operations and no radiotherapy compared with clinically presenting cases; there were fewer cases with active disease and hypopituitarism at last follow-up. When comparing AIPmut and AIPneg cases, AIPmut patients were more often males, younger, more often had GH excess, pituitary apoplexy, suprasellar extension, and more patients required multimodal therapy, including radiotherapy. AIPmut patients (n = 136) with GH excess were taller than AIPneg counterparts (n = 650). Conclusions Prospectively diagnosed AIPmut patients show better outcomes than clinically presenting cases, demonstrating the benefits of genetic and clinical screening. AIP-related pituitary disease has a wide spectrum ranging from aggressively growing lesions to stable or indolent disease course

Severe gynecomastia due to anti androgens intake: A case report and literature review

Gynecomastia is the most bothersome side effect in men taking antiandrogens. It is exceptionally severe and distressing physically and mentally as in the reported case. A man, aged 63, with a history of a well-treated macroprolactinoma, was referred in 2004 for gynecomastia that appeared after treatment by microsurgery, radiotherapy and flutamide for a lesion suspected to be prostate cancer. Clinical examination was normal except for huge enlargement of the breasts. Mammography and breasts MRI did not show any tumor. There was not any metastasis of the supposed prostate cancer and prostatic acid phosphates were within normal ranges. Hormonal exploration showed subclinical hypogonadism [testosterone: 7.4 ng/ml (n: 3-9), FSH: 14.9 mu/ml (n: 0.7-11) and LH: 9.7 mu/ml (n: 0.8-7.6)]. Testes ultrasounds were normal. Radiological and hormonal adrenal explorations were normal [Cortisol: 76 ng/ml (n: 50-250), DHEA-S: 59 μg/ml (n: 50-560), E2:40.2 pg/ml (n < 50)]. Body scan was normal too. The discussed etiologies were post radiation subclinical hypogonadism, and treatment with anti androgens. After flutamide withdraw, there was not any sign of prostate cancer recurrence, and gynecomastia decreased significantly, but did not disappear probably because of fibrosis

Diabetic retinopathy in acromegaly

Introduction: Although growth hormone (GH) has been implicated in the pathogenesis of diabetic retinopathy (DR), DR is deemed to be rare in patients with GH excess. Our aim was to study its prevalence in subjects with acromegaly suffering from diabetes mellitus (DM), to analyze its characteristics, and to look for predictive factors such as age at diagnosis, GH concentration and duration, DM duration, DM control, and family background. Materials and Methods: Forty patients with acromegaly and DM (21 males, 19 females), median age = 50 years, underwent a systematic ophthalmological examination with dilated funduscopy to seek diabetic retinopathy. Results: Among this population, 05 (12.5%) had DR. It was at an early stage or background retinopathy in 3 cases and at a more advanced stage or proliferative retinopathy in 2 cases. We did not find any correlation with age at diagnosis, GH levels and duration, DM duration and family history of DM, but poor glycemic control seems to play a role although statistical analysis showed borderline significance. Conclusion: From this study, we conclude that prevalence of DR in patients with acromegaly is 12.5%, and it is slight or moderate. Among studied factors, only poor glycemic control seems to be implicated in its development

Pituitary Adenomas in Multiple Endocrine Neoplasias Type1 and Other Endocrine Neoplasias Syndromes

Multiple Endocrine Neoplasias (MEN) are very rare genetic syndromes. Pituitary adenomas (PA) are usually sporadic, but can be observed in MEN type 1 and in other genetic syndromes such as Carney’s complex syndrome, MEN type 4 (MEN4), and some hereditary pheochromocytomas/paragangliomas syndromes (HPPS).Our aim was to analyze PA’s frequency and characteristics in aforementioned syndromes observed in our department.Material and Methods: The retrospective study analyzed frequency and characteristics of PA associated to typical and atypical MENs. We excluded incomplete files and MEN2, as research for PA was not systematic, and we looked for MEN2 in PA too. The patients did not undergo genetic testing.Results: Among ten hereditary syndromes (six MEN1 and four atypical MENs: either NEM4 or HPPS), we observed eight PA =80%. Four PA were associated with MEN1 and four with non-classical MENs. PA revealed MENs in four cases. PA median height was 19.88mm (7-50). Six/eight were macro tumors (≥1cm in height), with cavernous sinus invasion in two. PA types were prolactinomas (two), somatotroph adenomas (two), gonadotroph adenoma (one) and non-secreting tumors (three). For the follow up, only two out of six treated patients achieved remission.Conclusion: In this series, PA were frequent (80%) in MEN1 and non-classical MENs. Macro adenomas and secreting tumors were prevailing with a variable aggressiveness. These syndromes genetically determined should have systematic genetic screening to specify MENs types and for rapid diagnosis and early management of affected patients and their families

Diabetes mellitus in elderly

Diabetes mellitus (DM) frequency is a growing problem worldwide, because of long life expectancy and life style modifications. In old age (≥60–65 years old), DM is becoming an alarming public health problem in developed and even in developing countries as for some authors one from two old persons are diabetic or prediabetic and for others 8 from 10 old persons have some dysglycemia. DM complications and co-morbidities are more frequent in old diabetics compared to their young counterparts. The most frequent are cardiovascular diseases due to old age and to precocious atherosclerosis specific to DM and the most bothersome are visual and cognitive impairments, especially Alzheimer disease and other kind of dementia. Alzheimer disease seems to share the same risk factors as DM, which means insulin resistance due to lack of physical activity and eating disorders. Visual and physical handicaps, depression, and memory troubles are a barrier to care for DM treatment. For this, old diabetics are now classified into two main categories as fit and independent old people able to take any available medication, exactly as their young or middle age counterparts, and fragile or frail persons for whom physical activity, healthy diet, and medical treatment should be individualized according to the presence or lack of cognitive impairment and other co-morbidities. In the last category, the fundamental rule is "go slowly and individualize" to avoid interaction with poly medicated elder persons and fatal iatrogenic hypoglycemias in those treated with sulfonylureas or insulin

Feminizing adrenocortical tumors: Literature review

Feminizing adrenal tumors (FAT) are extremely rare tumors prevailing in males. Clinical manifestations are gynecomastia and/or other hypogonadism features in adults. They are rarer in pediatric population and their main manifestation is peripheral sexual precocity. In women genital bleeding, uterus hypertrophy, high blood pressure and/or abdomen mass may be the only manifestations. On the biological point, estrogen overproduction with or without increase in other adrenal hormones are the main abnormalities. Radiological examination usually shows the tumor, describes its limits and its eventual metastases. Adrenal and endocrine origins are confirmed by biochemical assessments and histology, but that one is unable to distinguish between benign and malignant tumors, except if metastases are already present. Immunostaining using anti-aromatase antibodies is the only tool that distinguishes FAT from other adrenocortical tumors. Abdominal surgery is the best and the first line treatment. For large tumors (≥10 cm), an open access is preferred to coeliosurgery, but for the small ones, or when the surgeon is experienced, endoscopic surgery seems to give excellent results. Surgery can be preceded by adrenolytic agents such as ortho paraprime dichloro diphenyl dichloroethane (Mitotane), ketoconazole or by aromatase inhibitors, but till now there is not any controlled study to compare the benefit of different drugs. New anti-estrogens can be used too, but their results need to be confirmed in malignant tumors resistant to classical chemotherapy and to conventional radiotherapy. Targeted therapy can be used too, as in other adrenocortical tumors, but the results need to be confirmed

General seizures revealing macro-adenomas secreting prolactin or prolactin and growth hormone in men

Background: Epilepsy is a heterogeneous condition with numerous etiologies. Pituitary tumors are rarely responsible for generalized convulsions except when they are very large. Apart from anecdotic cases, only one study concerning epilepsy frequency in male macroprolactinomas is available in Medline. Our aim was to analyze epilepsy frequency and conditions under which seizures appear and disappear in men harboring macroprolactinomas or somatolactotroph adenomas. Materials and Methods: We retrospectively analyzed 90 men with macro-adenomas (>1 cm) secreting prolactin (PRL) (n = 82) or both PRL and growth hormone (n = 8) to look for generalized seizures. We took into account familial and personal medical history, clinical examination, routine and hormonal analyzes, and radiological assessment based on cerebral magnetic resonance imaging. Results: Between 1992 and 2012, we collected eight cases (8.9%): Seven were hospitalized for recent generalized seizures; one had epilepsy after conventional radiotherapy given in 1992 because of neurosurgery failure and resistance to bromocriptine. Their median age was 33.75 years (22-58), median PRL was 9,198 ng/ml and median tumor height was 74 mm (41-110). The temporal lobe was invaded in six cases. After tumor reduction, epilepsy disappeared and never relapsed after a follow-up varying between 1 and 20 years. Conclusion: Epilepsy, which is a life-threatening condition, can be the first presentation in men with prolactinomas or somatolactotroph adenomas, especially those involving the supra sellar area, and the brain. Convulsions can also appear after radiotherapy. That one should be avoided, if possible, before tumor reduction by surgery or medical treatment