Djeho, the Egyptian God's dancer with dwarfism from the thirtieth dynasty.

This manuscript presents some artistic and medical considerations about a representation of an individual with apparent dwarfism. He was found in Saqqara by the British Egyptologist James Edward Quibell, in 1910/11. The naked figure of this individual, Djeho, is carved in profile on the lid of his sarcophagus. He has a height of 120 cm and has characteristic clinical features suggesting achondroplasia.

[The treatments of hyperthyroidism]. / Vignette thérapeutique de l'étudiant. Les traitements des hyperthyroïdies.

The clinician can access to a panel of therapeutic options to treat hyperthyroidism. Drugs, nuclear medicine and surgery can be used to take care of patients. Quite often, different options can be proposed to the same patient. The choice will be made based on each individual case : the presence of comorbidities, the urgency of the situation, the familial context and the patient's wishes. In this paper we will review the main therapeutic options. We will then discuss the key points that will allow to choose the most appropriate treatment.

Le traitement de l'hyperthyroïdie fait appel à un éventail de solutions allant des médicaments à la chirurgie en passant par la médecine nucléaire. Souvent, plusieurs options sont possibles dans une situation donnée. Le choix peut se faire en fonction de chaque contexte particulier : comorbidités, urgence, entourage familial et choix personnels. Dans cette vignette, nous passons en revue les grands axes thérapeutiques et leurs spécificités. Nous insistons ensuite sur les points qui permettent de décider du traitement.

[Thyroiditis]. / Les thyroïdites.

A thyroiditis is an inflammatory disease of the thyroid whether autoimmune, infectious or drug-induced. Autoimmune thyroid diseases (including Hashimoto's thyroiditis and Graves' disease) are the most frequent of all autoimmune pathologies. The clinical presentation and history are often revealing of the pathology and its etiology. Complementary examinations allow to confirm the diagnosis and to follow the evolution of the disease. Sometimes the disease could have a mixed presentation associating two different causes (like a mixed autoimmunity for Graves and Hashimoto diseases). In these cases, the treatment options are not always straightforward and may need to be adapted with the clinical evolution.

: Les thyroïdites désignent, au sens large, toutes les pathologies inflammatoires de la thyroïde, qu'elles soient auto-immunes, infectieuses ou médicamenteuses. Dans les maladies auto-immunes, les thyroïdites auto-immunes, dont la maladie de Hashimoto et la maladie de Basedow, sont les plus communes. Le tableau clinique et l'anamnèse sont parfois très révélateurs de la pathologie et de son étiologie. Les examens complémentaires permettent de confirmer l'hypothèse diagnostique et de suivre l'évolution de la maladie. Parfois, le tableau est moins typique avec des formes mixtes associant deux entités (comme une maladie de Basedow et de Hashimoto). Le diagnostic est, dans ces cas, moins évident et la prise en charge thérapeutique peut nécessiter une adaptation dans le temps.

[Subclinical hyperthyroidism]. / Vignette diagnostique de l'étudiant. Hyperthyroïdie fruste.

We describe a case of subclinical hyperthyroidism in a 77 years-old patient. This presentation, even if not clinically extreme, could lead to a decrease in the quality of life, but also to cardiac arrhythmia. This could also initiate more serious complications. We describe in the clinical story some of the signs that should draw suspicion of subacute hyperthyroidism. We recall factors that could potentially delay the diagnosis. Finally, we describe the use of different biological tests, ultrasound imaging and nuclear medicine.

Nous décrivons le tableau clinique d'une hyperthyroïdie fruste chez un patient de 77 ans. Ce tableau, même fruste, peut diminuer la qualité de vie et être à l'origine de troubles du rythme cardiaque. Des complications plus graves peuvent survenir dans ce contexte. Nous décrivons, dans ce cas clinique, quelques-uns des signes qui doivent faire suspecter une hyperthyroïdie fruste. Nous rappelons, ensuite, quelques facteurs qui sont susceptibles d'être à l'origine d'un diagnostic tardif. Nous décrivons, finalement, l'apport des différents examens biologiques, échographiques et de médecine nucléaire.

[Neuroendocrine neoplasms : a new era to the top of multidisciplinarity !] / Néoplasies neuroendocrines : une nouvelle ère a l'apogée de la multidisciplinarité !

Neuroendocrine neoplasms are histologically defined by a common neuroendocrine cellular phenotype. These are still considered as rare tumours even though their incidence is increasing. Heterogeneity is everywhere whether in the localization of the primitive cancer, the clinical presentation, the histological classification, the prognosis, as well as in therapeutic options, which clearly justifies specialized multidisciplinary care. Heterogeneity and scarcity explain the still fragmented nature of knowledge in this domain. Thanks to an increase in incidence, a desire for standardization of classification as well as the arrival of major therapeutic advances, such as vectorized internal radiotherapy, the future of neuroendocrine neoplasia seems more than promising and exciting. In our daily clinical practice at CHU Liège, we hope to bring our stone to the building by listing as many cases as possible in national and/or international databases, by centralizing therapeutic discussions within specific multidisciplinary concertations and by participating in multicenter study protocols.

Les néoplasies neuroendocrines sont définies histologiquement par un phénotype cellulaire neuroendocrine commun. Ces néoplasies sont toujours considérées comme des tumeurs rares, bien que leur incidence soit en constante augmentation. L'hétérogénéité est omniprésente, que ce soit dans la localisation du cancer primitif, la présentation clinique, la classification histologique, le pronostic ainsi que dans les diverses options thérapeutiques, justifiant impérativement une prise en charge pluridisciplinaire spécialisée. Cette hétérogénéité et cette rareté expliquent que les connaissances soient parcellaires. Grâce à une majoration d'incidence, une volonté d'uniformisation de classification ainsi que l'arrivée d'avancées thérapeutiques majeures, telles que la radiothérapie interne vectorisée, l'avenir des néoplasies neuroendocrines semble plus que prometteur et palpitant. En pratique clinique quotidienne au CHU de Liège, nous espérons apporter notre pierre à l'édifice en recensant un maximum de cas dans des bases de données nationales et/ou internationales, en centralisant les discussions thérapeutiques au sein de concertations multidisciplinaires dédiées et en participant à des protocoles d'études cliniques multicentriques.

Discordant biological parameters of remission in acromegaly do not increase the risk of hypertension or diabetes: a study with the Liege Acromegaly Survey database.

PURPOSE: Acromegaly is a rare disease due to growth hormone (GH)-secreting pituitary adenoma. GH and IGF-1 levels are usually congruent, indicating either remission or active disease; however, a discrepancy between GH and IGF-1 may occur. We aimed to evaluate the outcome of diabetes mellitus (DM) and hypertension (HT) in acromegalic patients with congruent GH and/or IGF-1 levels vs. discordant biochemical parameters. METHODS: Retrospective analysis of the data of 3173 patients from the Liege Acromegaly Survey (LAS) allowed us to include 190 patients from 8 tertiary referral centers across Europe, treated by surgery, with available data concerning DM and HT both at diagnosis and at the last follow-up (LFU). We recorded the number of anti-HT and anti-DM drugs used at the first evaluation and at LFU for every patient. RESULTS: Ninety-nine patients belonged to the REM group (concordant parameters), 65 patients were considered as GHdis (high random GH/controlled IGF-1), and 26 patients were considered as IGF-1dis (high IGF-1/controlled random GH). At diagnosis, 72 patients (37.8%) had HT and 54 patients had DM (28.4%). There was no statistically significant difference in terms of the number of anti-HT and anti-DM drugs at diagnosis versus LFU (mean duration: 7.3 ± 4.5 years) between all three groups. CONCLUSION: The long-term outcome of DM and HT in acromegaly does not tend to be more severe in patients with biochemical discordance in comparison with patients considered as in remission on the basis of concordant biological parameters, suggesting that patients with biochemical discordance do not require a closer follow-up.

[Endocrine consequences of immune checkpoint inhibitors]. / Répercussions endocriniennes des immunothérapies.

Immune checkpoints inhibitors have fundamentally changed the management of oncologic patients. These treatments consist of monoclonal antibodies directed against CTLA-4 (cytotoxic T-lymphocyte antigen 4), PD-1 (programmed cell death protein-1) and PD-L1 (one of its ligands). By blocking these receptors or ligands, the antibodies reverse the immune tolerance induced by the cancerous cell on the T-lymphocyte and favour lymphocytic reactivation and anti-tumor activity. Immune tolerance to auto-antigens is maintained with the help of these checkpoints. Targeting them can lead to auto-immune side effects. These latter mostly impact the cutaneous and digestive system, but the endocrine glands are not spared. In this article, we provide monitoring and treatment algorithms for these endocrine immune side effects. An early diagnosis followed by the appropriate treatment would reduce their negative impact on the oncologic care.

Les inhibiteurs des checkpoints immunitaires ont considérablement changé la prise en charge des cancers. Ces thérapeutiques sont actuellement représentées par les anticorps monoclonaux anti-CTLA-4 (cytotoxic T-lymphocyte antigen 4), anti-PD-1 (programmed cell death protein-1) et anti-PD-L1 (un de ses ligands). En bloquant ces récepteurs ou ligands, les anticorps contrecarrent le freinage immunitaire instauré par la cellule cancéreuse sur le lymphocyte T et favorisent, alors, la réactivation du lymphocyte et son activité anti-tumorale. Ces checkpoints sont essentiels dans le maintien de la tolérance immune aux auto-antigènes. En les ciblant, des effets secondaires de type auto-immun peuvent apparaître. S'ils privilégient principalement le système cutané et digestif, les glandes endocrines n'en sont néanmoins pas oubliées. Dans cet article, nous suggérons des algorithmes de surveillance et de prise en charge de ces manifestations indésirables endocriniennes. Le diagnostic précoce de celles-ci et leur traitement adéquat permettraient de réduire leur impact négatif sur la prise en charge de la maladie cancéreuse.

A multivariable prediction model for pegvisomant dosing: monotherapy and in combination with long-acting somatostatin analogues.

BACKGROUND: Effective treatment of acromegaly with pegvisomant (PEGV), a growth hormone receptor antagonist, requires an appropriate dose titration. PEGV doses vary widely among individual patients, and various covariates may affect its dosing and pharmacokinetics. OBJECTIVE: To identify predictors of the PEGV dose required to normalize insulin-like growth factor I (IGF-I) levels during PEGV monotherapy and in combination with long-acting somatostatin analogues (LA-SSAs). DESIGN: Two retrospective cohorts (Rotterdam + Liège Acromegaly Survey (LAS), total n = 188) were meta-analyzed as a form of external replication to study the predictors of PEGV dosing in addition to LA-SSA, the LAS (n = 83) was used to study the predictors of PEGV monotherapy dosing. Multivariable regression models were used to identify predictors of the PEGV dose required to normalize IGF-I levels. RESULTS: For PEGV dosing in combination with LA-SSA, IGF-I levels, weight, height and age, were associated with the PEGV normalization dosage (P ≤ 0.001, P ≤ 0.001, P = 0.028 and P = 0.047 respectively). Taken together, these characteristics predicted the PEGV normalization dose correctly in 63.3% of all patients within a range of ±60 mg/week (21.3% within a range of ±20 mg/week). For monotherapy, only weight was associated with the PEGV normalization dose (P ≤ 0.001) and predicted this dosage correctly in 77.1% of all patients within a range of ±60 mg/week (31.3% within a range of ±20 mg/week). CONCLUSION: In this study, we show that IGF-I levels, weight, height and age can contribute to define the optimal PEGV dose to normalize IGF-I levels in addition to LA-SSA. For PEGV monotherapy, only the patient's weight was associated with the IGF-I normalization PEGV dosage.

[Old phenotype and new genotypes. Pituitary adenomas]. / VIEUX PHÉNOTYPE ET NOUVEAUX GÉNOTYPES. Actualités dans le domaine des adénomes hypophysaires.

Gigantism and acromegaly, usually caused by a pituitary adenoma linked inappropriate secretion of growth hormone (GH), are generally considered as very rare diseases, even if, according to some authors, their cumulative prevalence is about 1/5000. Starting from the historical case of a giant from Liège we shall describe the different types of GH pituitary adenomas and their pathophysiology. We shall particularly discuss rare forms of inherited GH secreting pituitary adenomas like the FIPA (familial inherited isolated pituitary adenomas) and the X-LAG (X linked acrogigantism), both described for the first time in Liège, in 2000 and 2014, respectively.

[Malabsorption of thyroid hormones ... or simply poor patient compliance?]. / Malabsorption des hormones thyroïdiennes ... ou simple manque de compliance?

We report the case of a patient presenting with L-thyroxine pseudomalabsorbtion, a figure in which patients are in a state of biological, and, frequently, clinical hypothyroidism secondary to a lack of adherence to substitutive thyroid treatment. We then review the different causes of true thyroid hormones malabsorption and the different approaches to these situations. We also suggest diagnostic and therapeutic attitudes for clinicians facing suspicious cases of hormone malabsorption.

[The endocrine effects of smoking]. / Le tabac et ses effets sur le système endocrinien.

Almost one third of men and women smoke in Belgium. Besides the well known tobacco's neck and cardiopulmonary systems adverse effects as well as associated neoplasms, today we recognize other deleterious consequences of tobacco on the neuroendocrine, thyroid and reproductive systems. Not only active smokers but also the fetus carried by a smoking mother is at risk for important health problems. Tobacco is a recognized risk factor of occurrence of ophtalmopathy. Some of the active components of tobacco as the thiocyanates are goitrogenic. Tobacco is a risk factor for men and women's infertility. Newborns from parents that smoke are at risk for sudden death. These consequences represent a major public health issue. A campaign for smoking cessation has been recently launched by the Federation of Public Health Service and the INAMI in Belgium.

[Acromegaly in the elderly]. / L'acromégalie du sujet âgé.

UNLABELLED: Multicentric registers such as The French Acromegaly Register provide data on rare disorders that are otherwise difficult to obtain, so avoiding extrapolation from limited data sets. This study focuses on clinical, hormonal and therapy characteristics of acromegaly in people over 70 years old. The objective was to compare this population with the youngest to disclose if the medical management was similar. PATIENTS AND METHODS: The data were obtained from the 30 centres that have registered patients in the Acromegaly Register since 1999. RESULTS: The register listed 644 acromegaly patients on 1st January 2005, of whom 68 (22 men and 46 women) were over 70 years old, independently of the diagnosis date of their disease. Their average age was 76.8 + or - 5 years (range: 70-95) and they had suffered from acromegaly for 11 + or - 6 years (compared to 7 years in those aged less than 70). Their BMI were similar. Diabetes and hypertension were more frequent than in younger acromegalic patients and in the general French population matched for age. Circulating GH and IGF-1 concentrations were lower than in the younger acromegalic patients on inclusion and 1 year after treatment. There was no significant difference in the tumor size. Only 44% of the patients over 70 underwent surgery, against 90% of patients under 70 years. However, the fractions of young and elderly patients with a controlled disease 1 year after inclusion were the same (51%). CONCLUSION: In the limits of the use of register, these data reveal a high prevalence of diabetes and hypertension in the eldest acromegalic patients. Despite much less frequent surgical intervention, patients' disease under control is equivalent to the younger population 1 year after the initial interview, confirming the effectiveness of the choices of treatment.

Biometrology of physical properties of skin in thyroid dysfunction.

OBJECTIVE: There is ample clinical evidence that skin is responsive to physiopathological levels of circulating thyroid hormones. The aim of the study was to assess some physical changes of the skin in the presence of moderate thyroid dysfunction. SETTING: University Hospital. PATIENTS AND METHODS: A total of 119 adults suffering from hypothyroidism or hyperthyroidism and 60 healthy controls were enrolled in this study. Hormonal dosages (TSH, fT3, fT4) were assessed in the serum. A series of biometrological assessments were also performed on the volar and dorsal aspects of the forearms. These included electrometric assessments (Nova Dermal Phase Meter, Corneometer), evaporimetry (Tewameter)), colorimetry (Mexameter), ultrasound shear wave propagation (Reviscometer) and squamometry X. Correlations were searched between each of the serum hormonal dosages and each of the biometrological parameters. RESULTS: The hormonal changes in the untreated patients with thyroid dysfunction were modest in intensity. A few outlier values with regard to the normal range were found for each biometrological parameter. No correlations were found between fT3 or fT4 and each of the physical parameters. By contrast, significant negative linear correlations were found between thyroid-stimulating hormone (TSH) and skin hydration measured by the Corneometer and the Nova DPM. CONCLUSION: This multipronged exploratory study shows that direct or indirect effects of TSH may influence the stratum corneum hydration. This correlation seemed very sensitive, as no other specific biophysical parameter was significantly correlated with the thyroid hormonal concentrations in the serum. However, our findings do not exclude the possibility of some other skin changes supervening in case of more severe thyroid dysfunction. The mechanism by which TSH alters the stratum corneum hydration is yet unknown.

[Thyroid nodules]. / Nodules de la thyroïde.

Thyroid nodules are commonly encountered in clinical practice. They are present in 4 to 7% of the population by neck palpation and 30 to 50% by ultrasonography. Most are benign and could be neglected by the clinician and his patient. However, 5% of nodules are malignant, requiring surgical treatment; therefore, an exhaustive evaluation is needed. The diagnostic approach includes physical examination, laboratory analysis, ultrasonography, radioisotope imaging, and fine needle aspiration. This article, based on the literature and the authors'experience, provides recommandations for thyroid nodule management.

An overview of the epidemiology and genetics of acromegaly.

Historical data indicate that pituitary tumors represent 10% of intracranial tumors, while adenomas are noted in approximately 14-23% of normal subjects on autopsy or magnetic resonance imaging (MRI). About 2.5% of these tumors stain positive for GH in histopathologic studies. In contrast, the prevalence of clinically diagnosed acromegaly is lower at 36-69 per million population. Ongoing studies indicate that the actual prevalence of acromegaly in the community may be higher than previous epidemiologic data suggest. Acromegaly can occur both sporadically and in the setting of familial conditions, such as multiple endocrine neoplasia type 1 (MEN1) and Carney complex (CNC). Isolated familial somatotropinoma has been described and newer data suggest that acromegaly may also occur in non-MEN1/CNC families in combination with other pituitary tumor phenotypes.

Extensive inflammatory pseudotumor of the pituitary.

A 40-yr-old female presented with an extensive lesion of the sellar area and the sphenoid sinus, spreading to the optic nerves and associated with pachymeningitis. Histological findings were consistent with an inflammatory pseudotumor, and steroid treatment allowed the disappearance of all the lesions. Inflammatory pseudotumors of the pituitary are very rare. This case appears unique with regard to the extension of the lesions and the dramatic response to medical treatment. The differential diagnosis of inflammatory lesions of the pituitary is difficult. It relies mainly on histological analysis and includes sarcoidosis, Wegener's granulomatosis, histiocytosis (Langerhans, Rosai-Dorfman, and Erdheim-Chester diseases) and lymphocytic hypophysitis.

ACTH silent adenoma shrinking under cabergoline.

OBJECTIVES: The authors present a case report that proposes the use of cabergoline treatment in silent ACTH adenoma, an unusual member of the heterogeneous group of the so-called clinically non-functioning pituitary adenomas. DESIGN: Following the clinical and radiological improvement of a recurrent silent ACTH adenoma in a 77-year-old patient treated with cabergoline (0.5 mg every 2 days for 2 years), in vitro studies of the original tumor were performed. METHODS: The original tumor from the patient was studied by in situ hybridization and dopamine D2 receptor autoradiography. It was compared with four macroprolactinomas and two macroadenomas from patients with Cushing's disease. RESULTS: The D2 receptor mRNA signal of the reported case was intense and of the same order of magnitude as that observed in control prolactinomas. Dopamine D2 receptor autoradiography was twice that of control corticotroph adenomas and was close to that observed in prolactinomas. CONCLUSIONS: This is the first description of an in vivo shrinkage of an ACTH silent adenoma under cabergoline. We demonstrate in vitro, the presence of D2 receptors in the primitive tumor in concentrations similar to those found in control prolactinomas. These results suggest that therapeutic trials with cabergoline might be undertaken in recurring cases of ACTH silent tumors and more generally, non-functioning pituitary adenomas.

[Primary hyperparathyroidism: etiology, diagnosis and treatment]. / Les hyperparathyroïdies primaires: étiologies, diagnostic et traitement.

Primary hyperparathyroidism is a not so infrequent disease that is often overlooked by physicians. Its incidence is estimated to be about 28 in 100.000 subjects, mainly women over seventy years old. Three to four percents of women over seventy are affected. Hyperparathyroidism can be isolated or be a component of a more complex syndrome like multiple endocrine neoplasms (MEN). Patients can be asymptomatic or present with symptoms like asthenia, hypertension or nephrolithiasis. The biological investigation requires the combined measurements of plasmatic ionized calcium and parathormone. In some cases, more specific explorations like calcium loading tests have to be performed in order to confirm the diagnosis.