Amyloid infiltration of endocrine glands has been reported, mostly in the thyroid, pancreas, adrenals, and testes, but affected patients do not frequently exhibit overt endocrine insufficiency. Here ...we report the case of a patient with complete anterior hypopituitarism probably due to a known systemic amyloidosis.
Our male Caucasian patient was diagnosed with Crohn's disease at the age of 22 years. At the age of 37, he developed secondary renal amyloidosis, which resulted in end-stage renal failure. He received a living-donor kidney transplant at the age of 57, without initial complication. Two months later, he developed extreme fatigue, weight loss, and dyspnea. A hormonal evaluation demonstrated complete anterior pituitary insufficiency. A pituitary magnetic resonance imaging was performed and showed a diffusely hypointense anterior gland on both T1-weighted and T2-weighted images with reduced gadolinium enhancement, highly suggestive of amyloid infiltration of the pituitary. Treatment was initiated with levothyroxine, orally administered hydrocortisone, and testosterone enanthate, rapidly allowing progressive marked clinical improvement and nearly complete resolution of symptoms.
Pituitary amyloid infiltration should be considered in patients with a known systemic amyloidosis who develop symptoms of hypopituitarism and magnetic resonance imaging features compatible with protein deposits.
The global obesity epidemic continues to rise worldwide. In this context, unraveling new interconnections between biological systems involved in obesity etiology is highly relevant. Dysregulation of ...the endocannabinoidome (eCBome) is associated with metabolic complications in obesity. This study aims at deciphering new associations between circulating endogenous bioactive lipids belonging to the eCBome and metabolic parameters in a population of overweight or obese individuals with metabolic syndrome. To this aim, we combined different multivariate exploratory analysis methods: canonical correlation analysis and principal component analysis, revealed associations between eCBome subsets, and metabolic parameters such as leptin, lipopolysaccharide-binding protein, and non-esterified fatty acids (NEFA). Subsequent construction of predictive regression models according to the linear combination of selected endocannabinoids demonstrates good prediction performance for NEFA. Descriptive approaches reveal the importance of specific circulating endocannabinoids and key related congeners to explain variance in the metabolic parameters in our cohort. Analysis of quartiles confirmed that these bioactive lipids were significantly higher in individuals characterized by important levels for aforementioned metabolic variables. In conclusion, by proposing a methodology for the exploration of large-scale data, our study offers additional evidence of the existence of an interplay between eCBome related-entities and metabolic parameters known to be altered in obesity.
Automated immunoassays used to evaluate thyroid function are vulnerable to different types of interference that can affect clinical decisions. This review provides a detailed overview of the six main ...types of interference known to affect measurements of thyroid stimulating hormone (TSH), free thyroxine (T4) and free triiodothyronine (T3): macro-TSH, biotin, antistreptavidin antibodies, anti-ruthenium antibodies, thyroid hormone autoantibodies, and heterophilic antibodies. Because the prevalence of some of these conditions has been reported to approach 1% and the frequency of testing for thyroid dysfunction is important, the scale of the problem might be tremendous. Potential interferences in thyroid function testing should always be suspected whenever clinical or biochemical discrepancies arise. Their identification usually relies on additional laboratory tests, including assay method comparison, dilution procedures, blocking reagents studies, and polyethylene glycol precipitation. Based on the pattern of thyroid function test alterations, to screen for the six aforementioned types of interference, we propose a detection algorithm, which should facilitate their identification in clinical practice. The review also evaluates the clinical impact of thyroid interference on immunoassays. On review of reported data from more than 150 patients, we found that ≥50% of documented thyroid interferences led to misdiagnosis and/or inappropriate management, including prescription of an unnecessary treatment (with adverse effects in some situations), inappropriate suppression or modification of an ongoing treatment, or use of unnecessary complementary tests such as an I123 thyroid scan. Strong interaction between the clinician and the laboratory is necessary to avoid such pitfalls.
Objectives We aimed to investigate the clinical, biochemical, histological and radiological characteristics as well as the response to somatostatin analogs (SSA) in a large cohort of acromegaly ...patients with a paradoxical GH response (PR) to oral glucose tolerance test (OGTT). Design Retrospective study. Methods Of 110 patients with acromegaly included in our study, 30 (PR+; 27%) had a paradoxical GH increase of more than 25% relative to basal GH levels during OGTT. Results At diagnosis, PR+ patients were older than PR− patients (52 ± 16 years vs 44 ± 14 years, P < 0.05) and had smaller pituitary tumors (40% microadenomas vs 19%, P < 0.05), which were less often invasive (17% vs 35%, P < 0.05), overall more secreting (insulin-like growth factor-1 (IGF-1)/tumoral surface: 2.35 ULN/cm2 (0.28–9.06) vs 1.08 (0.17–7.87), P = 0.011), and more often hypointense on T2-weighted MRI (92% vs 48%, P = 0.001). While the rate of remission after surgery was similar in the two groups (69%), a better response to SSA treatment was observed in PR+ patients, either before (IGF-1 reduction of > 50% after 3–6 months in 77% vs 49%, P = 0.023) or after surgery (normalization of IGF-1 in 100% vs 44%, P = 0.011). Conclusions Our study demonstrates that in acromegaly, a paradoxical GH increase during OGTT is associated with particular features of somatotroph adenomas and with a better prognosis in terms of response to SSA.
Cabergoline is a new long-acting dopamine agonist that is
very effective and well tolerated in patients with pathological
hyperprolactinemia. The aim of this study was to examine, in a very
large ...number of hyperprolactinemic patients, the ability to normalize
PRL levels with cabergoline, to determine the effective
dose and tolerance, and to assess the effect on clinical symptoms,
tumor shrinkage, and visual field abnormalities. We also evaluated the
effects of cabergoline in a large subgroup of patients
with bromocriptine intolerance or -resistance.
We retrospectively reviewed the files of 455 patients (102 males and
353 females) with pathological hyperprolactinemia treated with
cabergoline in 9 Belgian centers. Among these patients,
41% had a microadenoma; 42%, a macroadenoma; 16%, idiopathic
hyperprolactinemia; and 1%, an empty sella. The median pretreatment
serum PRL level was 124 μg/L (range, 16–26,250 μg/L). A subgroup
of 292 patients had previously been treated with
bromocriptine, of which 140 showed
bromocriptine intolerance and 58 showed
bromocriptine resistance.
Treatment with cabergoline normalized serum PRL levels in
86% of all patients: in 92% of 244 patients with idiopathic
hyperprolactinemia or a microprolactinoma and in 77% of 181
macroadenomas. Pretreatment visual field abnormalities normalized in
70% of patients, and tumor shrinkage was seen in 67% of cases. Side
effects were noted in 13% of patients, but only 3.9% discontinued
therapy because of side effects. The median dose of
cabergoline at the start of therapy was 1.0 mg/week but
could be reduced to 0.5 mg/week once control was achieved. Patients
with a macroprolactinoma needed a higher median
cabergoline dose, compared with those with idiopathic
hyperprolactinemia or a microprolactinoma: 1.0 mg/week
vs. 0.5 mg/week, although a large overlap existed
between these groups. Twenty-seven women treated with
cabergoline became pregnant, and 25 delivered a healthy
child. One patient had an intended abortion and another a miscarriage.
In the patients with bromocriptine intolerance,
normalization of PRL was reached in 84% of cases, whereas in the
bromocriptine-resistant patients, PRL could be normalized
in 70%.
We confirmed, in a large-scale retrospective study, the high efficacy
and tolerability of cabergoline in the treatment of
pathological hyperprolactinemia, leaving few patients with unacceptable
side effects or inadequate clinical response. Patients with idiopathic
hyperprolactinemia or a microprolactinoma, on average, needed only half
the dose of cabergoline as those with macroprolactinomas
and have a higher chance of obtaining PRL normalization.
Cabergoline also normalized PRL in the majority of
patients with known bromocriptine intolerance or
-resistance. Once PRL secretion was adequately controlled, the dose of
cabergoline could often be significantly decreased, which
further reduced costs of therapy.
Summary A 26-year-old woman presented with severe postpartum headaches. Magnetic resonance imaging (MRI) revealed a symmetric, heterogeneous enlargement of the pituitary gland. Three months later, ...she developed central diabetes insipidus. A diagnosis of postpartum hypophysitis was suspected and corticosteroids were prescribed. Six months later, the pituitary mass showed further enlargement and characteristics of a necrotic abscess with a peripheral shell and infiltration of the hypothalamus. Transsphenoidal surgery was performed, disclosing a pus-filled cavity which was drained. No bacterial growth was observed, except a single positive blood culture for Staphylococcus aureus, considered at that time as a potential contaminant. A short antibiotic course was, however, administered together with hormonal substitution for panhypopituitarism. Four months after her discharge, severe headaches recurred. Pituitary MRI was suggestive of a persistent inflammatory mass of the sellar region. She underwent a new transsphenoidal resection of a residual abscess. At that time, the sellar aspiration fluid was positive for Staphylococcus aureus and she was treated with antibiotics for 6 weeks, after which she had complete resolution of her infection. The possibility of a pituitary abscess, although rare, should be kept in mind during evaluation for a necrotic inflammatory pituitary mass with severe headaches and hormonal deficiencies. Learning points: The possibility of a pituitary abscess, although rare, should be kept in mind during evaluation for a necrotic inflammatory pituitary mass with severe headaches and hormonal deficiencies. In a significant proportion of cases no pathogenic organism can be isolated. A close follow-up is necessary given the risk of recurrence and the high rate of postoperative pituitary deficiencies.
Pituitary incidentaloma Constantinescu, Stefan Matei; Maiter, Dominique
La Presse médicale (1983),
December 2021, 2021-Dec, 2021-12-00, 20211201, Letnik:
50, Številka:
4
Journal Article
Recenzirano
Pituitary incidentalomas (PI) are lesions of the pituitary region discovered fortuitously by imaging for reasons unrelated to pituitary disease. They range from small cysts to large invasive ...adenomas. All over the world, improvements in the quality and availability of radiological examinations are leading to an increase in the discovery of PI.
In the last four decades, significant advances have been made in the understanding of PI. Autopsy studies have shown that about 10% of deceased individuals harbour a PI, most often a non-functioning microadenoma. In contrast, modern patient series showed that among PIs that come to endocrinological attention, a significant proportion are macroadenomas, and many patients suffer from asymptomatic or pauci-symptomatic endocrine or ophthalmologic disturbances. Other than adenomas, empty sella, Rathke's cleft cyst, craniopharyngioma and meningioma are the most frequent types of PIs.
About 10% of micro-incidentalomas and 25% of macro-incidentalomas grow over time. Most cases can be managed conservatively by mere surveillance. Follow-up is necessary in all patients with macroadenoma, but uncertainty remains for microadenomas as to the extent of endocrinological work-up as well as the necessity and duration of follow-up. Visual and endocrine anomalies constitute the most common indications for surgery. When needed, surgery yields better outcome in PIs than in symptomatic pituitary lesions.
Objective: To assess the impairment of quality of life (QoL), evaluated by the acromegaly QoL (AcroQoL) questionnaire, in patients with controlled and uncontrolled acromegaly. Design: Cross-sectional ...evaluation of AcroBel, a national observational registry of acromegalic patients newly diagnosed or in follow-up. Methods: Disease perception by the patients was evaluated by the disease-specific signs and symptoms score (SSS) and QoL was assessed by the AcroQoL questionnaire. Hormonal status was determined by central measurements of GH and IGF-I. Results: Patients (n = 291) had a median GH of 1.43 μg/l (0.65–3.03; IQR), a median IGF-I of 231 μg/l (150–367), and a mean IGF-I z-score of +1.91 (s.d. 2.21). The AcroQoL total score in the whole group was 67.1 (51.1–78.4), with a score of 65.6 (43.8–78.1) for the physical dimension, 67.9 (53.6–80.4) for the psychological dimension, 78.6 (64.3–89.3) for personal relations and 57.1 (39.3–75) for appearance. The median SSS was 3 (1–5). There was a negative correlation between both questionnaires (r = −0.478; P < 0.001). There was no correlation between AcroQoL score and biochemical markers of disease activity. When subdividing patients into groups of biochemical control according to GH and IGF-I levels, no difference could be established for either SSS or AcroQoL scores. Conclusions: The AcroQoL results from the AcroBel registry confirm the marked impairment of the patients’ QoL, especially in relation with appearance. A negative correlation between AcroQoL and SSS was confirmed. There was, however, no correlation between AcroQoL and biochemical markers of disease activity.
Abstract Objective Although numerous studies have shown that transsphenoidal surgery is the best initial treatment for Cushing disease offering 59–95% of success, fewer information is available on ...the long-term outcome in the subgroup of patients harboring ACTH-secreting macroadenomas. The aims of this study were to analyze our 10-year experience with transsphenoidal surgery in Cushing's disease and to examine whether remission rates were different between micro- and macroadenomas. Patients and methods Forty consecutive patients with proven Cushing's disease (28 microadenomas, 12 macroadenomas diameter: 10–25 mm, 3 patients with no visible adenoma at MRI) underwent transsphenoidal surgery (TSS) assisted by neuronavigation in our center between 1996 and 2007. The diagnosis was made using standard endocrinological criteria including bilateral inferior petrosal sinus sampling (BIPSS) with CRH stimulation in all patients with discordant or equivocal biochemical and radiological testing. Morning serum cortisol was measured during the first week postoperatively, and a complete endocrine evaluation was made in all patients at 6–8 weeks. Remission at follow-up was defined as a normal postoperative 24-h urinary free cortisol (UFC) or continued need for glucocorticoid hormone replacement after TSS. Results Overall, 32/40 patients (80%) were in remission after one or more TSS. Interestingly, a very good remission rate (92%) was observed in the subset of macroadenomas, similar to that found in the group of microadenomas (84%, NS), while no post-surgical remission was observed in the 3 patients with no visible adenoma at MRI ( p < 0.01). Of the 8 patients not in remission after repeated TSS surgery, 3 underwent radiation therapy and three had bilateral adrenalectomy, allowing remission of their hypercortisolism. There was minor morbidity and no death. Conclusion While our overall results are in accordance with other published series, we show here that ACTH-secreting pituitary macroadenomas are usually not associated with a bad outcome, in contrast with patients with no visible adenoma at preoperative MRI.
Cabergoline is a new, long acting, dopamine agonist that is more
effective and better tolerated than bromocriptine in patients with
hyperprolactinemia. Because dopamine agonists still have a place in ...the
medical management of acromegaly, cabergoline might be a useful
treatment.
We, therefore, evaluated the effect of long term administration of
cabergoline in a large group of unselected acromegalic patients.
Sixty-four patients were included in a multicenter, prospective, open
labeled study. A subgroup of 16 patients had GH-/PRL-cosecreting
pituitary adenomas. Cabergoline was started at a dose of 1.0 mg/week
and was gradually increased until normalization of plasma insulin-like
growth factor I (IGF-I) levels, occurrence of unacceptable
side-effects, or a maximal weekly dose of 3.5 mg (7.0 mg in 1 case) was
reached.
Treatment with cabergoline suppressed plasma IGF-I below 300 μg/L in
39% of cases and between 300–450 μg/L in another 28%. With
pretreatment plasma IGF-I concentrations less than 750 μg/L, a
suppression of IGF-I below 300 μg/L was obtained in 53% of cases,
and a suppression between 300–450 μg/L was obtained in another 32%.
By contrast, with pretreatment plasma IGF-I concentrations above 750μ
g/L, only 17% of cases showed a suppression of IGF-I below 300μ
g/L, and there was IGF-I suppression between 300–450 μg/L in
another 21%. In GH-/PRL-cosecreting adenomas, 50% of cases suppressed
plasma IGF-I levels below 300 μg/L, and another 31% did so between
300–450 μg/L, in contrast to only 35% and 27%, respectively, in
GH-secreting adenomas.
Similar results were obtained concerning the secretion of GH. Tumor
shrinkage was demonstrated in 13 of 21 patients, with a mass reduction
by more than half in 5 GH-/PRL-cosecreting adenomas. Except for slight
gastrointestinal discomfort and orthostatic hypotension in a few
patients at the beginning of therapy, cabergoline treatment was well
tolerated. Only 2 patients stopped medication because of nausea. The
weekly dose of cabergoline ranged between 1.0–1.75 mg. A further
increase in the dose was only effective in 1 GH-/PRL-cosecreting
adenoma.
The results of this study suggest that cabergoline is an effective,
well tolerated therapy that should be considered in the management of
acromegaly, especially if the pituitary adenoma cosecretes GH and PRL
or if pretreatment plasma IGF-I levels are below 750 μg/L.
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