Prevalence and incidence of prolactinomas are approximately 50 per 100,000 and 3–5 new cases/100,000/year. The pathophysiological mechanism of hyperprolactinemia-induced gonadotropic failure involves ...kisspeptin neurons. Prolactinomas in males are larger, more invasive and less sensitive to dopamine agonists (DAs). Macroprolactin, responsible for pseudohyperprolactinemia is a frequent pitfall of prolactin assay.
DAs still represent the primary therapy for most prolactinomas, but neurosurgery has regained interest, due to progress in surgical techniques and a high success rate in microprolactinoma, as well as to some underestimated side effects of long-term DA treatment, such as impulse control disorders or impaired quality of life. Recent data show that the suspected effects of DAs on cardiac valves in patients with prolactinomas are reassuring. Finally, temozolomide has emerged as a valuable treatment for rare cases of aggressive and malignant prolactinomas that do not respond to all other conventional treatments.
Endocrine Aspects of Obstructive Sleep Apnea Attal, Pierre; Chanson, Philippe
The journal of clinical endocrinology and metabolism,
2010-February, Letnik:
95, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Context: Some endocrine and metabolic disorders are associated with a high frequency of obstructive sleep apnea (OSA), and treatment of the underlying endocrine disorder can improve and occasionally ...cure OSA. On the other hand, epidemiological and interventional studies suggest that OSA increases the cardiovascular risk, and a link between OSA and glucose metabolism has been suggested, via reduced sleep duration and/or quality.
Evidence Acquisition: We reviewed the medical literature for key articles through June 2009.
Evidence Synthesis: Some endocrine and metabolic conditions (obesity, acromegaly, hypothyroidism, polycystic ovary disease, etc.) can be associated with OSA. The pathophysiological mechanisms of OSA in these cases are reviewed. In rare instances, OSA may be improved or even cured by treatment of underlying endocrine disorders: this is the case of hypothyroidism and acromegaly, situations in which OSA is mainly related to upper airways narrowing due to reversible thickening of the pharyngeal walls. However, when irreversible skeletal defects and/or obesity are present, OSA may persist despite treatment of endocrine disorders and may thus require complementary therapy. This is also frequently the case in patients with obesity, even after substantial weight reduction.
Conclusions: Given the potential neurocognitive consequences and increased cardiovascular risk associated with OSA, specific therapy such as continuous positive airway pressure is recommended if OSA persists despite effective treatment of its potential endocrine and metabolic causes.
“Apropos of sleep, that sinister adventure of all our nights, we might say that men go to bed daily with an audacity that would be incomprehensible if we did not know that it is the result of ignorance of the danger.”
Charles Baudelaire, in “Fusées, IX”
Given the potential neurocognitive consequences and increased cardiovascular risk associated with OSA, specific therapy, such as continuous positive airway pressure, is recommended if OSA persists despite effective treatment of its potential endocrine and metabolic causes.
Acromegaly is controlled in one-third of cases by cabergoline single-agent therapy and in more than half of cases when cabergoline is added to failing somatostatin analogue therapy.
Context:
...Cabergoline is widely considered to be poorly effective in acromegaly.
Objective:
The aim of this study was to obtain a more accurate picture of the efficacy of cabergoline in acromegaly, both alone and in combination with somatostatin analogs.
Design:
We systematically reviewed all trials of cabergoline therapy for acromegaly published up to 2009 in four databases (PubMed, Pascal, Embase, and Google Scholar). We identified 15 studies (11 prospective) with a total of 237 patients; none were randomized or placebo-controlled. A meta-analysis was conducted on individual data (n = 227).
Results:
Cabergoline was used alone in nine studies. Fifty-one (34%) of the 149 patients achieved normal IGF-I levels. In multivariate analysis, the decline in IGF-I was related to the baseline IGF-I concentration (β = 1.16; P <0.001), treatment duration (β = 0.28; P < 0.001), and baseline prolactin concentration (β = −0.18; P = 0.01), and with a trend toward a relation with the cabergoline dose (β = 0.38; P =0.07). In five studies, cabergoline was added to ongoing somatostatin analog treatment that had failed to normalize IGF-I. Forty patients (52%) achieved normal IGF-I levels. The change in IGF-I was significantly related to the baseline IGF-I level (β = 0.74; P < 0.001) but not to the dose of cabergoline, the duration of treatment, or the baseline prolactin concentration.
Conclusion:
This meta-analysis suggests that cabergoline single-agent therapy normalizes IGF-I levels in one third of patients with acromegaly. When a somatostatin analog fails to control acromegaly, cabergoline adjunction normalizes IGF-I in about 50% of cases. This effect may occur even in patients with normoprolactinemia.
Other Pituitary Conditions and Pregnancy Chanson, Philippe
Endocrinology and metabolism clinics of North America,
09/2019, Letnik:
48, Številka:
3
Journal Article
Recenzirano
Diagnosis of lymphocytic hypophysitis occurring in the peripartum period is based on clinical and neuroradiological data and does not require a biopsy. Its course is generally spontaneously favorable ...in terms of mass effect but may require the administration of corticosteroids or even transsphenoidal resection. The course of pituitary deficiencies is highly variable; some cases recover over time, whereas others persist indefinitely. Sheehan syndrome is very rare in developed countries. Because agalactia and amenorrhea are often neglected, the diagnosis is generally delayed. Diabetes insipidus occurring in late pregnancy is caused by the increased placental production of vasopressinase and disappears after delivery.
Multiple endocrine neoplasia type 1 (MEN1) is a rare syndrome characterized by the co-occurrence of primary hyperparathyroidism, duodenopancreatic neuroendocrine tumours (NETs) and/or pituitary ...adenomas. MEN1 can predispose patients to other endocrine and non-endocrine tumours, such as cutaneous tumours, central nervous system tumours and breast cancer. Endocrine tumours in patients with MEN1 differ from sporadic tumours in that they have a younger age at onset, present as multiple tumours in the same organ and have a different clinical course. Therefore, patients with overt MEN1 and those who carry a MEN1 mutation should be offered tailored biochemical and imaging screening to detect tumours and evaluate their progression over time. Fortunately, over the past 10 years, knowledge about the clinical phenotype of these tumours has markedly progressed, thanks to the implementation of national registries, particularly in France and the Netherlands. This Review provides an update on the clinical management of MEN1-related tumours. Epidemiology, the clinical picture, diagnostic work-up and the main lines of treatment for MEN1-related tumours are summarized. Controversial therapeutic aspects and issues that still need to be addressed are also discussed. Moreover, special attention is given to MEN1 manifestations in children and adolescents.
Besides their growth-promoting properties, GH and IGF-1 regulate a broad spectrum of biological functions in several organs, including the kidney. This review focuses on the renal actions of GH and ...IGF-1, taking into account major advances in renal physiology and hormone biology made over the last 20 years, allowing us to move our understanding of GH/IGF-1 regulation of renal functions from a cellular to a molecular level. The main purpose of this review was to analyze how GH and IGF-1 regulate renal development, glomerular functions, and tubular handling of sodium, calcium, phosphate, and glucose. Whenever possible, the relative contributions, the nephronic topology, and the underlying molecular mechanisms of GH and IGF-1 actions were addressed. Beyond the physiological aspects of GH/IGF-1 action on the kidney, the review describes the impact of GH excess and deficiency on renal architecture and functions. It reports in particular new insights into the pathophysiological mechanism of body fluid retention and of changes in phospho-calcium metabolism in acromegaly as well as of the reciprocal changes in sodium, calcium, and phosphate homeostasis observed in GH deficiency. The second aim of this review was to analyze how the GH/IGF-1 axis contributes to major renal diseases such as diabetic nephropathy, renal failure, renal carcinoma, and polycystic renal disease. It summarizes the consequences of chronic renal failure and glucocorticoid therapy after renal transplantation on GH secretion and action and questions the interest of GH therapy in these conditions.
Acromegaly is an acquired disorder related to excessive production of growth hormone (GH) and characterized by progressive somatic disfigurement (mainly involving the face and extremities) and ...systemic manifestations. The prevalence is estimated at 1:140,000-250,000. It is most often diagnosed in middle-aged adults (average age 40 years, men and women equally affected). Due to insidious onset and slow progression, acromegaly is often diagnosed four to more than ten years after its onset. The main clinical features are broadened extremities (hands and feet), widened thickened and stubby fingers, and thickened soft tissue. The facial aspect is characteristic and includes a widened and thickened nose, prominent cheekbones, forehead bulges, thick lips and marked facial lines. The forehead and overlying skin is thickened, sometimes leading to frontal bossing. There is a tendency towards mandibular overgrowth with prognathism, maxillary widening, tooth separation and jaw malocclusion. The disease also has rheumatologic, cardiovascular, respiratory and metabolic consequences which determine its prognosis. In the majority of cases, acromegaly is related to a pituitary adenoma, either purely GH-secreting (60%) or mixed. In very rare cases, acromegaly is due to ectopic secretion of growth-hormone-releasing hormone (GHRH) responsible for pituitary hyperplasia. The clinical diagnosis is confirmed biochemically by an increased serum GH concentration following an oral glucose tolerance test (OGTT) and by detection of increased levels of insulin-like growth factor-I (IGF-I). Assessment of tumor volume and extension is based on imaging studies. Echocardiography and sleep apnea testing are used to determine the clinical impact of acromegaly. Treatment is aimed at correcting (or preventing) tumor compression by excising the disease-causing lesion, and at reducing GH and IGF-I levels to normal values. Transsphenoidal surgery is often the first-line treatment. When surgery fails to correct GH/IGF-I hypersecretion, medical treatment with somatostatin analogs and/or radiotherapy can be used. The GH antagonist (pegvisomant) is used in patients that are resistant to somatostatin analogs. Adequate hormonal disease control is achieved in most cases, allowing a life expectancy similar to that of the general population. However, even if patients are cured or well-controlled, sequelae (joint pain, deformities and altered quality of life) often remain.
The exact physiological basis of acute growth hormone (GH) suppression by oral glucose is not fully understood. Glucose-mediated increase in hypothalamic somatostatin seems to be the most plausible ...explanation. Attempts to better understand its underlying mechanisms are compromised by species disparities in the response of GH to glucose load. While in humans, glucose inhibits GH release, the acute elevation of circulating glucose levels in rats has either no effect on GH secretion or may be stimulatory. Likewise, chronic hyperglycemia alters GH release in both humans and rats nonetheless in opposite directions. Several factors influence nadir GH concentrations including, age, gender, body mass index, pubertal age, and the type of assay used. Besides the classical suppressive effects of glucose on GH release, a paradoxical GH increase to oral glucose may be observed in around one third of patients with acromegaly as well as in various other disorders. Though its pathophysiology is poorly characterized, an altered interplay between somatostatin and GH-releasing hormone has been suggested and a link with pituitary ectopic expression of glucose-dependent insulinotropic polypeptide receptor has been recently demonstrated. A better understanding of the dynamics mediating GH response to glucose may allow a more optimal use of the OGTT as a diagnostic tool in various conditions, especially acromegaly.
Abstract
Context
Inferior petrosal sinus sampling (IPSS) is used to diagnose Cushing’s disease (CD) when dexamethasone-suppression and CRH tests, and pituitary magnetic resonance imaging (MRI), are ...negative or give discordant results. However, IPSS is an invasive procedure and its availability is limited.
Objective
To test a noninvasive diagnostic strategy associated with 100% positive predictive value (PPV) for CD.
Design
Retrospective study.
Setting
Two university hospitals.
Patients
A total of 167 patients with CD and 27 patients with ectopic ACTH-syndrome investigated between 2001 and 2016.
Main Outcome Measure(s)
Performance of a strategy involving the CRH and desmopressin tests with pituitary MRI followed by thin-slice whole-body computed tomography (CT) scan in patients with inconclusive results.
Results
Using thresholds of a cortisol increase > 17% with an ACTH increase > 37% during the CRH test and a cortisol increase > 18% with an ACTH increase > 33% during the desmopressin test, the combination of both tests gave 73% sensitivity and 98% PPV of CD. The sensitivity and PPV for pituitary MRI were 71% and 99%, respectively. CT scan identified 67% EAS at presentation with no false-positives. The PPV for CD was 100% in patients with positive responses to both tests, with negative pituitary MRI and CT scan. The Negative Predictive Value was 100% in patients with negative responses to both tests, with negative pituitary MRI and positive CT scan. Using this strategy, IPPS could have been avoided in 47% of patients in whom it is currently recommended.
Conclusions
In conjunction with expert radiologic interpretation, the non-invasive algorithm studied significantly reduces the need for IPSS in the investigation of ACTH-dependent Cushing’s syndrome.
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